Biomark Insights
· 2017 · PMID 28890654
·
Full text
Monocyte chemoattractant protein-1 (MCP-1) overproduction from inflamed adipose tissue is a major contributor to obesity-related metabolic syndromes. 3T3-L1 embryonic fibroblasts were cultured and differentiated into adi...Monocyte chemoattractant protein-1 (MCP-1) overproduction from inflamed adipose tissue is a major contributor to obesity-related metabolic syndromes. 3T3-L1 embryonic fibroblasts were cultured and differentiated into adipocytes using an established protocol. Adipocytes were treated with lipopolysaccharide (LPS) to induce inflammation and thus MCP-1 release. At the same time, varying concentrations of chondroitin sulfate (CS) were added in a physiologically relevant range (10-200 µg/mL) to determine its impact on MCP-1 release. Chondroitin sulfate, a natural glycosaminoglycan of connective tissue including the cartilage extracellular matrix, was chosen on the basis of our previous studies demonstrating its anti-inflammatory effect on macrophages. Because the main action of MCP-1 is to induce monocyte migration, cultured THP-1 monocytes were used to test whether CS at the highest physiologically relevant concentration could inhibit cell migration induced by human recombinant MCP-1. Chondroitin sulfate (100-200 µg/mL) inhibited MCP-1 release from inflamed adipocytes in a dose-dependent manner ( < .01, 95% confidence interval [CI]: -5.89 to -3.858 at 100 µg/mL and < .001, 95% CI: -6.028 to -3.996 at 200 µg/mL) but had no effect on MCP-1-driven chemotaxis of THP-1 monocytes. In summary, CS could be expected to reduce macrophage infiltration into adipose tissue by reduction in adipocyte expression and release of MCP-1 and as such might reduce adipose tissue inflammation in response to pro-inflammatory stimuli such as LPS, now increasingly recognized to be relevant in vivo.
de Geus SW, Baart VM, Boonstra MC
… +8 more, Kuppen PJ, Prevoo HA, Mazar AP, Bonsing BA, Morreau H, van de Velde CJ, Vahrmeijer AL, Sier CF
Biomark Insights
· 2017 · PMID 28690396
·
Full text
The urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for various malignancies. The aim of this study is to assess the prognostic value of uPAR expression in neoplastic an...The urokinase plasminogen activator receptor (uPAR) has been proposed as a potential prognostic factor for various malignancies. The aim of this study is to assess the prognostic value of uPAR expression in neoplastic and stromal cells of patients with pancreatic adenocarcinoma. Urokinase plasminogen activator receptor expression was determined by immunohistochemistry in 122 pancreatic ductal adenocarcinomas. Kaplan-Meier and Cox regression analyses were used to determine the association with survival. Respectively 66%, 82% and 62% of patients with pancreatic cancer expressed uPAR in neoplastic cells, stromal, and in both combined. Multivariate analysis showed a significant inverse association between uPAR expression in both neoplastic and stromal cells and overall survival. The prognostic impact of uPAR in stromal cells is substantial, but not as pronounced as that of uPAR expression in neoplastic cells. This study suggests a role for uPAR as a biomarker to single out higher risk subgroups of patients with pancreatic cancer.
Biomark Insights
· 2017 · PMID 28659713
·
Full text
This review discusses the current state of biomarker discovery for the purposes of diagnostics and therapeutic monitoring. We underscore relevant challenges that have defined the gap between biomarker discovery and meani...This review discusses the current state of biomarker discovery for the purposes of diagnostics and therapeutic monitoring. We underscore relevant challenges that have defined the gap between biomarker discovery and meaningful clinical use. We highlight recent advancements in and propose a way to think about future biomarker development.
Monti L, Morbidelli L, Bazzani L
… +1 more, Rossi A
Biomark Insights
· 2017 · PMID 28615922
·
Full text
Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and as...Blood-brain barrier (BBB) breakdown, inflammatory and immune cell activation, and chronic cerebral hypoperfusion are features of multiple sclerosis (MS). The aim is to determine the influence of endothelin-1 (ET1) and asymmetric dimethylarginine (ADMA) on cerebral circulation time (CCT) in patients with MS. In all, 64 patients with MS (39 relapsing-remitting [RR]-MS; 25 secondary progressive [SP]-MS subtype) and 37 controls (C) were studied. Cerebral circulation time was obtained by angiography. Plasmatic ET1 and ADMA were measured by enzyme-linked immunosorbent assay. Lesion load (LL) and brain volume (BV) were obtained by magnetic resonance imaging. Cerebral circulation time was correlated to ET1, ADMA, LL, BV, disease duration (DD), and Expanded Disability Status Scale (EDSS). In MS, both ET1 and ADMA were significantly higher than C ( < .0001); CCT was approximately 2 times lower than C ( < .0001) and significantly slower in SP than in RR-MS ( = .0215). Cerebral circulation time significantly correlated with ET1 in SP-MS ( = 0.38), whereas in RR-MS CCT significantly correlated with DD ( = 0.75). The LL, BV, and EDSS did not correlate with CCT. Endothelin-1 significantly influences CCT delay in SP-MS. Diversely, CCT in RR-MS is independent of ET1 and correlates significantly with DD. We conclude that in RR-MS, DD responds to neurovascular damage accumulation. It is supposed that high ET1 and ADMA levels stem from a protective response to early insults, aimed at opposing nitric oxide overproduction, whereas persistent pathological ET1 and ADMA levels translate into detrimental long-term effects, due to increased brain micro-vessel resistance.
Rauniyar N, Peng G, Lam TT
… +3 more, Zhao H, Mor G, Williams KR
Biomark Insights
· 2017 · PMID 28615921
·
Full text
A data-independent acquisition (DIA)/parallel reaction monitoring (PRM) workflow was implemented to identify improved ovarian cancer biomarkers. Data-independent acquisition on ovarian cancer versus control sera and lite...A data-independent acquisition (DIA)/parallel reaction monitoring (PRM) workflow was implemented to identify improved ovarian cancer biomarkers. Data-independent acquisition on ovarian cancer versus control sera and literature searches identified 50 biomarkers and indicated that apolipoprotein A-IV (ApoA-IV) is the most significantly differentially regulated protein. Parallel reaction monitoring with Targeted Ovarian Cancer Proteome Assay validated differential ApoA-IV expression and quantified 9 other biomarkers. Random Forest (RF) analyses achieved 92.3% classification accuracy and confirmed ApoA-IV as the leading biomarker. Indeed, all samples were classified correctly with an [ApoA-IV] breakpoint. The next best biomarkers were C-reactive protein, transferrin, and transthyretin. The Targeted Ovarian Cancer Proteome Assay suggests that ApoA-IV is a more reliable biomarker than had been determined by immunological assays and it is a better biomarker than ApoA-I, which is in the OVA1 test for ovarian cancer. This research provides a PRM/RF approach together with 4 promising biomarkers to speed the development of a clinical assay for ovarian cancer.
Gustafsson A, Ventorp F, Wisén AG
… +3 more, Ohlsson L, Ljunggren L, Westrin Å
Biomark Insights
· 2017 · PMID 28469403
·
Full text
Inflammation has been proposed to play a role in the generation of depressive symptoms. Previously, we demonstrated that patients with major depressive disorder (MDD) have increased plasma levels of the soluble form of t...Inflammation has been proposed to play a role in the generation of depressive symptoms. Previously, we demonstrated that patients with major depressive disorder (MDD) have increased plasma levels of the soluble form of the urokinase receptor (suPAR), a marker for low-grade inflammation. The aim of this study was to test the hypothesis that acute exercise would induce inflammatory response characterized by increased suPAR and elucidate whether patients with MDD display altered levels of suPAR in response to acute exercise. A total of 17 patients with MDD and 17 controls were subjected to an exercise challenge. Plasma suPAR (P-suPAR) was analyzed before, during, and after exercise. There was a significantly higher baseline P-suPAR in the patients with MDD, and the dynamic changes of P-suPAR during the exercise were significantly lower in the patients with MDD, compared with the controls. This study supports the hypothesis that an activation of systemic inflammatory processes, measured as elevated P-suPAR, is involved in the pathophysiology of depression. The study concludes that P-suPAR is influenced by acute exercise, most likely due to release from activated neutrophils.
Biomark Insights
· 2017 · PMID 28469402
·
Full text
MicroRNAs (miRNAs) regulate the expression of protein-coding genes and represent potential biomarkers for childhood acute lymphoblastic leukemia (ALL). However, information linking miRNAs with their messenger RNA (mRNA)...MicroRNAs (miRNAs) regulate the expression of protein-coding genes and represent potential biomarkers for childhood acute lymphoblastic leukemia (ALL). However, information linking miRNAs with their messenger RNA (mRNA) target genes modulating white blood cell (WBC) count is lacking. Here, we analyzed miRNAs and gene expression data from pediatric patients with ALL to identify a signature of miRNAs involved in ALL and their mRNA target genes, molecular networks, and biological pathways modulating WBC. We discovered a signature of miRNAs differentially expressed in ALL and a signature of mRNA target genes distinguishing patients with high WBC from patients with low WBC. In addition, we identified molecular networks and biological pathways, among them PI3/AKT, JAK/STAT, IL-17, TGF-β, apoptosis, IL-15, STAT3, IGF-1, FGF, mTOR, VEGF, NF-kB, and P53 signaling pathways, enriched for or targeted by miRNAs. The discovered miRNAs and their target genes and pathways represent potential clinically actionable biomarkers and therapeutic targets.
Trovato M, Campennì A, Giovinazzo S
… +2 more, Siracusa M, Ruggeri RM
Biomark Insights
· 2017 · PMID 28469401
·
Full text
The hepatocyte growth factor (HGF)/c-met axis plays a crucial role in cancer development by promoting cellular proliferation, motility, and morphogenesis, as well as angiogenesis. Different cellular distributions of both...The hepatocyte growth factor (HGF)/c-met axis plays a crucial role in cancer development by promoting cellular proliferation, motility, and morphogenesis, as well as angiogenesis. Different cellular distributions of both the ligand and the receptor in benign vs malignant lesions indicate this biological system as a candidate for a diagnostic biomarker of malignancy occurring in endocrine glands, such as the thyroid and pituitary. Furthermore, the HGF/c-met expression may help to identify a subset of patients eligible for potential targeted therapies with HGF/c-met inhibitors or antagonists in thyroid tumour, as well as in other malignancies. This may be relevant for iodine-refractory cancers, the treatment of which is still a major challenge. With this in mind, HGF/c-met expression in thyroid cancer tissue may be useful for prognostic and therapeutic stratification of patients.
Kristof J, Sakrison K, Jin X
… +6 more, Nakamaru K, Schneider M, Beckman RA, Freeman D, Spittle C, Feng W
Biomark Insights
· 2017 · PMID 28469400
·
Full text
In preclinical studies, heregulin () expression was shown to be the most relevant predictive biomarker for response to patritumab, a fully human anti-epidermal growth factor receptor 3 monoclonal antibody. In support of...In preclinical studies, heregulin () expression was shown to be the most relevant predictive biomarker for response to patritumab, a fully human anti-epidermal growth factor receptor 3 monoclonal antibody. In support of a phase 2 study of erlotinib ± patritumab in non-small cell lung cancer (NSCLC), a reverse-transcription quantitative polymerase chain reaction (RT-qPCR) assay for relative quantification of expression from formalin-fixed paraffin-embedded (FFPE) NSCLC tissue samples was developed and validated and described herein. Test specimens included matched FFPE normal lung and NSCLC and frozen NSCLC tissue, and -positive and -negative cell lines. Formalin-fixed paraffin-embedded tissue was examined for functional performance. Heregulin distribution was also analyzed across 200 NSCLC commercial samples. Applied Biosystems TaqMan Gene Expression Assays were run on the Bio-Rad CFX96 real-time PCR platform. Heregulin RT-qPCR assay specificity, PCR efficiency, PCR linearity, and reproducibility were demonstrated. The final assay parameters included the Qiagen FFPE RNA Extraction Kit for RNA extraction from FFPE NSCLC tissue, 50 ng of RNA input, and 3 reference (housekeeping) genes (, and ), which had expression levels similar to expression levels and were stable among FFPE NSCLC samples. Using the validated assay, unimodal distribution was confirmed across 185 evaluable FFPE NSCLC commercial samples. Feasibility of an RT-qPCR assay for the quantification of expression in FFPE NSCLC specimens was demonstrated.
Bennett MR, Pleasant L, Haffner C
… +6 more, Ma Q, Haffey WD, Ying J, Wagner M, Greis KD, Devarajan P
Biomark Insights
· 2017 · PMID 28469399
·
Full text
Idiopathic nephrotic syndrome (NS) is the most common glomerular disorder of childhood. Response to initial treatment with corticosteroids is an indicator of prognosis, as resistant patients often present more progressiv...Idiopathic nephrotic syndrome (NS) is the most common glomerular disorder of childhood. Response to initial treatment with corticosteroids is an indicator of prognosis, as resistant patients often present more progressive disease. In this cross-sectional pilot study, we set out to discover a panel of noninvasive biomarkers that could distinguish steroid-resistant nephrotic syndrome (SRNS) from steroid-sensitive nephrotic syndrome (SSNS). Information gleaned from such a panel could yield more individualized treatment plans and prevent unnecessary steroid exposure in patients unlikely to respond. Urine was collected from 50 pediatric patients diagnosed with idiopathic NS at Cincinnati Children's Hospital Medical Center. Isobaric tags for relative and absolute quantitation (iTRAQ) was used to discover 13 proteins that were differentially expressed in SSNS vs SRNS in a small 5 × 5 discovery cohort. Suitable assays were found for 9 of the 13 markers identified by iTRAQ and were used in a 25 SRNS × 25 SSNS validation cohort. Vitamin D-binding protein (VDBP), alpha-1 acid glycoprotein 1 (AGP1), alpha-1 acid glycoprotein 2 (AGP2), alpha-1-B glycoprotein (A1BG), fetuin-A, prealbumin, thyroxine-binding globulin and hemopexin, and alpha-2 macroglobulin were measured and combined with urine neutrophil gelatinase-associated lipocalin (NGAL), which had been previously shown to distinguish patients with SRNS. Urinary VDBP, prealbumin, NGAL, fetuin-A, and AGP2 were found to be significantly elevated in SRNS using univariate analysis, with area under the receiver operating characteristic curves (AUCs) ranging from 0.65 to 0.81. Multivariate analysis revealed a panel of all 10 markers that yielded an AUC of 0.92 for identification of SRNS. A subset of 5 markers (including VDBP, NGAL, fetuin-A, prealbumin, and AGP2) showed significant associations with SRNS and yielded an AUC of 0.85.
Hicks C, Ramani R, Sartor O
… +4 more, Bhalla R, Miele L, Dlamini Z, Gumede N
Biomark Insights
· 2017 · PMID 28469398
·
Full text
High-throughput genotyping has enabled discovery of genetic variants associated with an increased risk of developing prostate cancer using genome-wide association studies (GWAS). The goal of this study was to associate G...High-throughput genotyping has enabled discovery of genetic variants associated with an increased risk of developing prostate cancer using genome-wide association studies (GWAS). The goal of this study was to associate GWAS information of patients with primary organ-confined and metastatic prostate cancer using gene expression data and to identify molecular networks and biological pathways enriched for genetic susceptibility variants involved in the 2 disease states. The analysis revealed gene signatures for the 2 disease states and a gene signature distinguishing the 2 patient groups. In addition, the analysis revealed molecular networks and biological pathways enriched for genetic susceptibility variants. The discovered pathways include the androgen, apoptosis, and insulinlike growth factor signaling pathways. This analysis established putative functional bridges between GWAS discoveries and the biological pathways involved in primary organ-confined and metastatic prostate cancer.
Biomark Insights
· 2017 · PMID 28469397
·
Full text
Leptomeningeal carcinomatosis (LC) is a rare and mainly secondary site of metastasis in solid tumors. In gastric cancer (GC), it is associated with a devastating prognosis, lacking an efficient and standardized treatment...Leptomeningeal carcinomatosis (LC) is a rare and mainly secondary site of metastasis in solid tumors. In gastric cancer (GC), it is associated with a devastating prognosis, lacking an efficient and standardized treatment approach. We report a case of primary manifestation of LC due to metastatic GC with rapid deterioration and refractory course to conventional and intrathecal chemotherapy. We review the literature and discuss the therapeutic challenges.
Meguid NA, Ghozlan SAS, Mohamed MF
… +6 more, Ibrahim MK, Dawood RM, Din NGBE, Abdelhafez TH, Hemimi M, Awady MKE
Biomark Insights
· 2017 · PMID 28469396
·
Full text
The molecular basis of the pathophysiological role of oxidative stress in autism is understudied. Herein, we used polymerase chain reaction (PCR) array to analyze transcriptional pattern of 84 oxidative stress genes in p...The molecular basis of the pathophysiological role of oxidative stress in autism is understudied. Herein, we used polymerase chain reaction (PCR) array to analyze transcriptional pattern of 84 oxidative stress genes in peripheral blood mononuclear cell pools isolated from 32 autistic patients (16 mild/moderate and 16 severe) and 16 healthy subjects (each sample is a pool from 4 autistic patients or 4 controls). The PCR array data were further validated by quantitative real-time PCR in 80 autistic children (55 mild/moderate and 25 severe) and 60 healthy subjects. Our data revealed downregulation in , and transcripts (1.5, 3.8, 1.2, 1.7, and 2.2, respectively; < .05 for all) in autistic group compared with controls. In addition, and exhibited 1.4- and 1.7-fold downregulation, respectively, in severe autistic patients when compared with mild/moderate group ( = .005 and .0008, respectively). This study helps in a better understanding of the underlying biology and related genetic factors of autism, and most importantly, it presents suggested candidate biomarkers for diagnosis and prognosis purposes as well as targets for therapeutic intervention.
Andarieh MG, Zabihi E, Moslemi D
… +6 more, Delavar MA, Haji-Ahmadi M, Monfared AS, Jorsaraei SGA, Ghasemi M, Esmaeilzadeh S
Biomark Insights
· 2017 · PMID 28469395
·
Full text
The Cytochrome P-4501B1 () Leu432Val polymorphism has been previously shown to be associated with some types of cancer and affects -mediated metabolism of various infertility drugs. To establish the frequency of Leu432V...The Cytochrome P-4501B1 () Leu432Val polymorphism has been previously shown to be associated with some types of cancer and affects -mediated metabolism of various infertility drugs. To establish the frequency of Leu432Val polymorphism among women with a history of infertility drug use, we studied the genotypes of 147 patients with breast cancer with a history of infertility and 150 cancer-free, infertile women (control group) in Northern Iran. A polymerase chain reaction-based restriction fragment length polymorphism assay was used to detect GG (Val/Val), CG (Leu/Val), and CC (Leu/Leu) genotype frequencies, which did not vary significantly between the 2 patient groups ( = .847). We established for the first time that the incidence of Leu432Val polymorphism is 46.6% among women with infertility history and breast cancer in Northern Iran. Finally, our results do not show any significant association between Leu432Val polymorphism and breast cancer in infertile women in this region, who have also received infertility treatment.
Schrijver IT, Kemperman H, Roest M
… +2 more, Kesecioglu J, de Lange DW
Biomark Insights
· 2017 · PMID 28469394
·
Full text
AIMS: This study investigated the ability of soluble platelet selectin (sP-selectin) to identify infection and predict 30-day mortality in patients with a systemic inflammatory response syndrome (SIRS) on the intensive c...AIMS: This study investigated the ability of soluble platelet selectin (sP-selectin) to identify infection and predict 30-day mortality in patients with a systemic inflammatory response syndrome (SIRS) on the intensive care unit. METHODS: Soluble platelet selectin levels were measured daily in the first 48 hours in patients presenting with SIRS. The outcome, proven infection, was established using predefined definitions. The 30-day mortality was retrospectively assessed. RESULTS: In a total of 313 patients with SIRS, sP-selectin levels were measured. Of these, 114 patients had proven infection on admission or developing during their intensive care unit (ICU) stay. Patients with proven infection had moderately higher levels of sP-selectin (147 ng/mL; interquartile range [IQR], 93.4-203 ng/mL) compared with noninfected patients (143.8 ng/mL; IQR, 89.6-194.7 ng/mL). This difference was not statistically significant ( = .072). However, in patients who were not admitted for infection (n = 235), sP-selectin levels were significantly related to the subsequent development of infection ( = .013). Soluble platelet selectin levels were particularly high in patients with abdominal sepsis and skin infections. Higher sP-selectin levels were associated with higher mortality (although not statistically significant, = .08). CONCLUSIONS: This study shows that in patients with SIRS not admitted for infection, sP-selectin levels are significantly related to the subsequent development of infection. Furthermore, patients with higher sP-selectin levels in the first 2 days of admission had higher 30-day mortality, although this association is not statistically significant. Therefore, we conclude that sP-selectin is a potential future biomarker for both mortality and infection in patients with SIRS, but more research is needed to confirm its prognostic role.
Pollott G, Brito A, Gardiner C
… +1 more, Lawson C
Biomark Insights
· 2016 · PMID 28008221
·
Full text
Cow's milk is economically important to the agricultural industry with the nutritive value of milk being routinely measured. This does not give full insight into normal mammary tissue turnover during the course of lactat...Cow's milk is economically important to the agricultural industry with the nutritive value of milk being routinely measured. This does not give full insight into normal mammary tissue turnover during the course of lactation, which could be important for both an understanding of milk production and animal welfare. We have previously demonstrated that submicron particles, including extracellular vesicles (EVs), can be measured in unprocessed cow's milk by flow cytometry and that they correlate with stage of lactation. A number of different techniques are available to measure EVs and other milk-derived particles. The purpose of this study was to compare two different methodologies and the value of fluorescent staining for the phospholipid phosphatidylserine (PS), which is exposed on the surface of EVs (but not other milk-derived particles). We used two different flow cytometers and nanotracker analysis to detect milk-derived particles in whole and skimmed milk samples. Our findings indicate significant correlation, after staining for PS, suggesting potential for larger multicenter studies in the future.
Beumer IJ, Persoon M, Witteveen A
… +9 more, Dreezen C, Chin SF, Sammut SJ, Snel M, Caldas C, Linn S, van 't Veer LJ, Bernards R, Glas AM
Biomark Insights
· 2016 · PMID 27980389
·
Full text
BACKGROUND: MammaPrint® is a microarray-based gene expression test cleared by the US Food and Drug Administration to assess recurrence risk in early-stage breast cancer, aimed to guide physicians in making neoadjuvant an...BACKGROUND: MammaPrint® is a microarray-based gene expression test cleared by the US Food and Drug Administration to assess recurrence risk in early-stage breast cancer, aimed to guide physicians in making neoadjuvant and adjuvant treatment decisions. The increase in the incidence of invasive lobular carcinomas (ILCs) over the past decades and the modest representation of ILC in the MammaPrint development data set calls for a stratified survival analysis dedicated to this specific subgroup. STUDY AIM: The current study aimed to validate the prognostic value of the MammaPrint test for breast cancer patients with early-stage ILCs. MATERIALS AND METHODS: Univariate and multivariate survival associations for overall survival (OS), distant metastasis-free interval (DMFI), and distant metastasis-free survival (DMFS) were studied in a study population of 217 early-stage ILC breast cancer patients from five different clinical studies. RESULTS AND DISCUSSION: A significant association between MammaPrint High Risk and poor clinical outcome was shown for OS, DMFI, and DMFS. A subanalysis was performed on the lymph node-negative study population. In the lymph node-negative study population, we report an up to 11 times higher change in the diagnosis of an event in the MammaPrint High Risk group. For DMFI, the reported hazard ratio is 11.1 (95% confidence interval = 2.3-53.0). CONCLUSION: Study results validate MammaPrint as an independent factor for breast cancer patients with early-stage invasive lobular breast cancer. Hazard ratios up to 11 in multivariate analyses emphasize the independent value of MammaPrint, specifically in lymph node-negative ILC breast cancers.
Biomark Insights
· 2016 · PMID 27980388
·
Full text
It is encouraging to observe that a search for publications on "asymmetric dimethylarginine (ADMA)" in PubMed, as updated on June 2016, yielded >2500 items, 24 years after a splendid paper published by Vallance et al in...It is encouraging to observe that a search for publications on "asymmetric dimethylarginine (ADMA)" in PubMed, as updated on June 2016, yielded >2500 items, 24 years after a splendid paper published by Vallance et al in which the authors proposed that ADMA accumulation could be a cardiovascular risk factor in chronic kidney diseases. ADMA is the endogenous inhibitor of nitric oxide synthase and is related to endothelial dysfunction, which plays an important role in vascular damage elicited by various cardiometabolic risk factors. Although current knowledge suggests that ADMA has critical central roles in renal diseases, there are still unexplained details. The present article aims to provide a review on ADMA and its relation as a biomarker in nephrologic diseases. We aimed to systematize articles in which ADMA levels were assessed in order to clarify its role in many diseases and establish its reference values in different populations.
Pérez SB, Rodríguez-Fanjul J, García IJ
… +2 more, Hernando JM, Iriondo Sanz M
Biomark Insights
· 2016 · PMID 27840575
·
Full text
OBJECTIVES: To assess the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) in newborns after cardiothoracic surgery (CS), with and without cardiopulmonary bypass, and to assess whether PCT was better than CRP...OBJECTIVES: To assess the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) in newborns after cardiothoracic surgery (CS), with and without cardiopulmonary bypass, and to assess whether PCT was better than CRP in identifying sepsis in the first 72 hours after CS. PATIENTS AND METHODS: This is a prospective study of newborns admitted to the neonatal intensive care unit after CS. INTERVENTIONS: PCT and CRP were sequentially drawn 2 hours before surgery and at 0, 12, 24, 48, and 72 hours after surgery. RESULTS: A total of 65 patients were recruited, of which 14 were excluded because of complications. We compared the kinetics of PCT and CRP after CS in bypass and non-bypass groups without sepsis; there were no differences in the PCT values at any time (24 hours, = 0.564; 48 hours, = 0.117; 72 hours, = 0.076). Thirty-five patients needed bypass, of whom four were septic (11.4%). Significant differences were detected in the PCT values on comparing the septic group to the nonseptic group at 48 hours after cardiopulmonary bypass ( = 0.018). No differences were detected in the CRP values in these groups. A suitable cutoff for sepsis diagnosis at 48 hours following bypass would be 5 ng/mL, with optimal area under the curve of 0.867 (confidence interval 0.709-0.958), < 0.0001, and sensitivity and specificity of 87.5% (29.6-99.7) and 72.6% (53.5-86.4), respectively. CONCLUSION: This is a preliminary study but PCT seems to be a good biomarker in newborns after CS. Values over 5 ng/mL at 48 hours after CS should alert physicians to the high risk of sepsis in these patients.
Biomark Insights
· 2016 · PMID 27594783
·
Full text
Cisplatin is a known antitumor drug, but its mechanisms of action are not fully elucidated. In this research, we studied the anticancer potential of cisplatin at doses of 1, 2, or 3 µM using HL-60 cells as a test model....Cisplatin is a known antitumor drug, but its mechanisms of action are not fully elucidated. In this research, we studied the anticancer potential of cisplatin at doses of 1, 2, or 3 µM using HL-60 cells as a test model. We investigated cisplatin effects at the molecular level using RNA sequencing, cell cycle analysis, and apoptotic assay after 24, 48, 72, and 96 hours of treatment. The results show that many genes responsible for molecular and cellular functions were significantly altered. Cisplatin treatment also caused the cells to be arrested at the DNA synthesis phase, and as the time increases, the cells gradually accumulated at the sub-G1 phase. Also, as the dose increases, a significant number of cells entered into the apoptotic and necrotic stages. Altogether, the data show that low doses of cisplatin significantly impact the viability of HL-60 cells, through modulation of gene expression, cell cycle, and apoptosis.