Laboratories require customized feedback on improving biomarker testing practices. A workshop was organized for laboratories that participated in a European external quality assessment scheme to resolve issues related to the estimation of neoplastic cell percentage and tissue quality for RAS testing for colorectal cancer. An interactive course about tissue quality took place to stress the importance of the pre-analytical phase. During a microscopic session, five H&E stained tumor tissue slides were discussed and neoplastic cell percentages estimated. Participants included 4 pathologists, 3 molecular biologists, a technologist and a clinical geneticist from 7 laboratories. In six laboratories, tumor contents are checked routinely by visual estimation by the pathologist. The average difference between the lowest and highest estimation was 22%. During the workshop the importance of the pre-analytical phase was stressed and feedback was provided. Such initiatives can contribute in improving biomarker testing standards in Europe
Background: Measure of serum 17β-Estradiol is essential to understand physiology, development and health of reproductive processes in both sexes. Commercially immunoassays are not enough sensitive and accurate to assess low concentrations of E2. Purpose of this study was to compare a new sensitive immunoassay for estradiol measurement with respect to method current in our laboratory and to evaluate the performance of the new method. Methods: Four pools of patient sera with E2 concentrations close to clinical decision values were prepared. To test the repeatability of new method the 5x5 protocol was used and CVs were calculated. To evaluate the performance of new method, 50 samples with E2 concentrations covering the whole measurable interval were selected and assayed. Linearity dilution, LoB (Limit of Blank) and LoD (Limit of Detection) were determined. Results: The new assay showed good total repeatability demonstrated by low CV values, and good linear relationship with respect to current method (R=0.9926) as demonstrated by linear regression. Non-parametric regression showed for the new method a slight constant and proportional systematic error that, however, resulted not significant from difference plot analysis, with a general tendency to overestimate results for the current method. Performances of the new method resulted acceptable within the maximum admissible error derived from the literature, and a good linearity over a wide range of dilutions was showed. LoD value confirmed an amelioration in measurement of low estradiol. Conclusion: In conclusion, sensitive assay is suitable to replace the method used in our laboratory with significant improvement in the measurement of low serum estradiol levels.
Approximately 50%-80%of cancer patients have been reported to result in a devasting syndrome such as cancer cachexia (CC) and at least 20% patients reach the death [1]. Sarcopenia accompanying with muscle loss shows the most clinically relevant phenotypic feature of CC, such as asthenia, fatigue, impaired physiologic function, reduced tolerance to treatments, resulting in impaired quality of life and shorter survival. Such wasting syndromes as sarcopenia are shown in 20%-70% cases depending on the tumor type. Accordingly, reversion of CC and sarcopenia is of most importance and interest. In addition, high serum IL-6 has been reported to result in cancer metastases, invasion and resulting in CC [2,3]. Early detection of such sarcopenia syndromes is clinically most important. If sarcopenia can be precedently predicted, better treatment strategies will be possible. It is well-known that sarcopenia is accompanied by increased levels of inflammation factors TNF-alpha and IL-6 [4]. It has been reported that activation of the IL-6/STAT3 pathway also plays a causative role in the pathogenesis of cancer cachexia, one of the most distressing complications associated with the development of ovarian cancer [5]. Indeed, cachexia usually accompanies the development of ascites and chemoresistance in the most advanced stages of the disease [6]. The majority of advanced gynecologic cancer (GC) patients develop cachexia, which is a major contributor of morbidity and mortality in these patients. Cachexia is primarily responsible for body and muscle weight loss and correlates with tumor burden, increased proinflammatory cytokine levels, fatigue, and reduced response to chemotherapy and radio-therapy [7]. Patients presenting with advanced stage GC often show large tumor and ascites burden that, in turn, results into severe malnourishment because of decreased oral intake and compromised bowel functions. Despite its significant negative impact on quality of life, no effective treatment is currently available for GC-related cachexia. Indeed, muscle loss and low skeletal muscle attenuation are often detected in women undergoing primary debulking surgery for the treatment of GCs. Along the same line, recent evidence suggests that baseline sarcopenia represents one of the most accurate prognostic factors for survival in advanced GC and during chemotherapy treatment [8]. Clinically, we find out that elevation of serum IL-6 in patients with gynecologic cancers is varied by effect of the adjuvant chemotherapy.
Dysregulation of c-FLIP (cellular FADD-like IL-1β-converting enzyme inhibitory protein) has been shown in several diseases including cancer, Alzheimer's disease, and chronic obstructive pulmonary disease (COPD). c-FLIP is a critical anti-cell death protein often overexpressed in tumors and hematological malignancies and its increased expression is often associated with a poor prognosis. c-FLIP frequently exists as long (c-FLIPL) and short (c-FLIPS) isoforms, regulates its anti-cell death functions through binding to FADD (FAS associated death domain protein), an adaptor protein known to activate caspases-8 and -10 and links c-FLIP to several cell death regulating complexes including the death-inducing signaling complex (DISC) formed by various death receptors. c-FLIP also plays a critical role in necroptosis and autophagy. Furthermore, c-FLIP is able to activate several pathways involved in cytoprotection, proliferation, and survival of cancer cells through various critical signaling proteins. Additionally, c-FLIP can inhibit cell death induced by several chemotherapeutics, anti-cancer small molecule inhibitors, and ionizing radiation. Moreover, c-FLIP plays major roles in aiding the survival of immunosuppressive tumor-promoting immune cells and functions in inflammation, Alzheimer's disease (AD), and chronic obstructive pulmonary disease (COPD). Therefore, c-FLIP can serve as a versatile biomarker for cancer prognosis, a diagnostic marker for several diseases, and an effective therapeutic target. In this article, we review the functions of c-FLIP as an anti-apoptotic protein and negative prognostic factor in human cancers, and its roles in resistance to anticancer drugs, necroptosis and autophagy, immunosuppression, Alzheimer's disease, and COPD.
Background: Oxidative stress is an imbalance between reactive species and antioxidants production, leading to protein, DNA and lipid damage. The aim of this study was to evaluate the oxidative stress levels in buccal cells of ten non-shisha and heavy shisha smokers using MAWI iSWAB protein tubes. Materials and findings: The presence of S-glutathionylation, NOX2 and iNOS was analyzed in buccal cells of ten non-smokers and ten heavy shisha smokers using MAWI i-SWAB protein tubes, knowing that they were able to detect previously several protein oxidation biomarkers (S-nitrosylation and nitrotyrosine). Proteins concentrations were assessed by Bradford assay then western blot method was used to analyze the presence of the different proteins of interest. Conclusion: Results confirmed the findings about the ability of these tubes to detect S-nitrosylation, nitrotyrosine, as well as S-glutathionylation. Results showed also the presence of immature NOX2 in human buccal cells equally. Levels of iNOS were the same in non-shisha and heavy shisha smokerss.
Background: Chromosomal translocations of the mixed-lineage leukemia gene (MLL; tMLL) correlate with resistance to therapy and an extremely poor prognosis for individuals with Acute Myeloid Leukemia (AML). The underlying mechanisms are still unknown. This study aims to identify the key genes and the potential molecular mechanisms involved in MLL rearrangement in AML using a bioinformatics approach. Methods: The gene expression profiles from 15 individuals with partial tandem duplication of the MLL gene (MLL-PTD)-AML and 10 tMLL-AML samples were downloaded from the Gene Expression Omnibus (GEO) database. The Differentially Expressed Genes (DEGs) were selected and functional enrichment analyses were performed. The Protein-Protein Interaction (PPI) network was established and visualized in Cytoscape. The hub genes were identified by CytoHubba and significant modules were screened out by Molecular Complex Detection (MCODE). Results: We categorized a total of 885 DEGs comprising 330 upregulated and 555 downregulated genes. The majority of DEGs were significantly enriched for calcium ion transmembrane transport, embryonic skeletal system morphogenesis and cell proliferation processes. Several pathways were enriched, including those associated with PI3K-Akt signaling and insulin resistance. We identified 32 hub genes and screened out 2 modules. Conclusion: The genes we have identified in this study may represent potential biomarkers for MLL-rearranged AML and contribute to the development of novel therapeutic strategies.
Aim of the study: To measure high-sensitive troponin (Access hsTnI) interidentical- instrument bias (DxI800 Beckman Coulter) in order to understand if it can compromise the interpretation of absolute delta value for rapid algorithms 0/1-0/3 hours. Materials and methods: One hundred fifty-nine lithium/heparin plasma samples were processed sequentially on three DxI800 (DxI1, DxI2, DxI3). The results given by the three instruments were analyzed as followed: DxI1 vs. DxI2, DxI1 vs. DxI3, DxI2 vs. DxI3. Statistical analysis was done using the Passing-Bablok regression, Bland-Altman test, and Cohen’s Kappa statistic. Results: PB regression did not show any significant deviation from linearity and no proportional nor constant differences were observed among instruments. Moreover, the mean absolute bias, even though among the three instruments the lowest 95%CI lower limit was -3.75 and the highest 95%CI upper limit was 3.92 ng/L, was within the acceptance limits (all results
Non-specific Inflammatory Bowel Diseases (IBD) are particularly troublesome diseases affecting the human digestive tract, in particular the intestine.These diseases manifest themselves in chronic intestinal inflammation that is difficult to control, with periods of uncontrolled exacerbations and self-reminiscent occurrences.Depending on the symptoms and their location in the human gastrointestinal tract, these diseases may occur in various forms.Among the two most common forms of these diseases, Ulcerative Colitis (UC), and Crohn's Disease (CD) can be distinguished.Although the underlying cause of activation as well as the subsequent development of these diseases is not clearly defined, these disorders are known to have autoimmune background.The pathogenesis of IBD is associated with chronic idiopathic, recurrent, inflammatory-mediated gastrointestinal inflammation.The disease may be caused by changes in genes caused by various factors or family genetic predisposition.Exposure to a range of environmental risk factors may lead to disease activation in susceptible individuals.Many of the various factors mentioned in the article, which people are exposed to in their lives, may influence the development of these diseases.
Acute aortic dissection remains the most common aortic catastrophe currently. It is significant to be on the alert for the recurrent aortic dissection. A 62-yearold woman with hypertension was admitted to the Emergency department with sudden intense back pain, profuse sweating and with the feeling of impending death for 3 hours. The surgeon of Peking University Shougang hospital conducted TEVAR in the first day after hospitalization and the back pain had lessened after the surgeon. The fourth day after hospitalization, the patient had Intermittent back pain. The recurrent dissection entry was found on the bottom of the thoracic artery stent-graft. The surgeon of Peking University Shougang hospital conducted the endovascular covered stent-graft repair of the abdominal aorta.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common neoplasm worldwide. Despite advances in treatment for HNSCC, the patient’s survival remains poor. Therefore, in order to improve HNSCC patient’s outcome, it is essential to explore novel biomarkers for predicting response to treatment. Herein, we state that the neutrophil to lymphocyte ratio (NLR) is a biomarker to predict the efficacy of chemoradiotherapy (CRT) in HNSCC patients and to predict the wound healing failure in head and neck reconstruction surgery. Although elevated pretreatment NLR was significantly correlated with poor response to CRT, lower preoperative NLR tended to exhibit a higher occurrence rate of posto-perative wound healing failure in HN reconstruction surgery. Thus, in case which HNSCC patient with lower NLR has remnant tumor after CRT, salvage surgery with microsurgical reconstruction might include a higher occurrence rate of postoperative wound complications than the present. Head and neck surgeons should take care of the possibility.
Heart failure (HF) is a global public health concern that continues to have a sufficient impact on morbidity, mortality and disability in developing ad developed countries. Contemporary diagnostic and prediction strategy bases on biomarker use, which helps improving individual prognostication and early verification of the disease. However, widely implementing biomarkers such as natriuretic peptides, and several new biomarkers (glectin-3, soluble ST2 and others) were not demonstrated strong ability to improve discriminative capacity in various HF phenotypes. In this context micro vesicle (MVs), which play a core role in the endogenous reparation, coagulation, inflammation, immunity and metabolic memory phenomenon, could be prospective biomarkers in HF with predictive ability. However, there is not yet strong evidence those immune phenotypes of MVs are important for prediction and development of several phenotypes of HF. The aim of the review: to summarize knowledge regarding the role of various MVs in diagnosis and prognosis of HF.
Cancer cells exhibit profound alterations in their metabolism.The process of increased aerobic glycolysis supports cell proliferation and promotes cancer progression via alteration of glucose, glutamine and lipid metabolism.In recent years, extensive efforts have been devoted to revealing the mechanisms underlying for metabolic alterations in cancer, thus products of intermediary metabolism has been a topic of considerable research interest over the past decades.Metabolomics is defined as the quantitative measurement of the dynamic multiparametric metabolites.Identification and quantification of intermediary metabolism by metabolomics can better understand the metabolic changes in tumors.Hence metabolic profiling may be of broad utility for investigating the metabolic pathways and molecular mechanism of carcinogenesis, and as the powerful tool to screen the potential biomarkers for the early diagnosis of human cancer and drug responsiveness.This review article will summarize the overview of metabolomics and the target identification in metabolic pathway by metabolomics, as well as the application in cancer diagnosis and prognosis.In addition, we also critically evaluating the limitation of this approach, and present the potential applications of metabolite profiling in development of novel therapeutic strategy for cancer and precision medicine.
MicroRNAs are small non-coding RNA molecules with a length of 20 to 25 nucleotides. As gene expression regulators, microRNAs can completely or not completely complementarily bind with mRNA to inhibit translation or degradate mRNA. Aberrant expression of microRNAs is closely related to the occurrence, development, metastasis and prognosis of prostate cancer. Some microRNAs may promote cancerization, while others are tumor suppressors. In this review, we summarized the expression profiles of microRNAs in recent years, in particular, the data obtained by large-scale high-throughput technologies. We also summed up microRNAs which had the potential to be biomarkers of prostate cancer, and the mechanisms of microRNAs in the developmental progression of prostate cancer. The review provided medical and scientific researchers with an overview of the status and role of microRNAs in prostate cancer. In short, we summarized the expression profiles of microRNAs discovered in recent years and their roles and mechanisms in the occurrence and development of prostate cancer.
Background: Reactive Oxygen Species (ROS) production has been established as an essential contributor in the development cardiotoxicity. The increase of ROS production simultaneously leads to the inhibition of anti-oxidant systems. Forkhead transcription factor O1 (FOXO1) plays an important role in regulating metabolism and oxidant stress. Clozapine was used to induce cardiotoxicity. Forskolin the well-known anti-oxidant and anti-inflammatory agent was used to modulate the effect on both FOXO1 gene and its target gene catalase and to what extent it may protect against clozapine-induced cardiotoxicity. Methods: The animals were classified into: control group, forskolin group; forskolin was administered for 8 weeks; clozapine group, and forskolin + clozapine group; forskolin was pre-administered for 5 weeks then continued along with clozapine for the last 3 weeks. RT-qPCR and gel electrophoresis were done. We analyzed the relation between FoxO1 gene and oxidative stress. Results: These effects are achieved by the ability of Forskolin to modulate the expression of Foxo-1 and catalase, the levels of CKMB, troponin I, GST, MDA, and TNF- α, Caspase-3 were decreased, histopathological changes were improved. Forskolin reduce cardiomyocytes damage, and improve cardiac function by decreasing oxidative stress. Conclusion: Forkolin with its biological activities and anti-oxidative effects control cardiotoxicity induced by ROS in addition to its anti-inflammatory activity. This may be considered as therapy in cardiac problems management.
Gastric Cancer (GC) is one of the most three reasons related to death caused by cancer, especially in East Asia area, where many people have been suffering in this disease. Although there are significant improvements in surgical techniques and medical standards, the five-year survival rate of GC patients is still low. Epithelial- Mesenchymal Transition (EMT) plays a key role in the process of metastasis, which is a biological process that epithelial cells lose their polarity and turn into mesenchymal phenotype. It also enjoys a potential effect on invasion and migration of multiple malignancies, including that of gastric cancer. Accumulating evidences in literature suggest that long noncoding RNAs (lncRNAs) play an important role in the process of EMT. In this review, roles of lncRNAs in GC EMT are highlighted and pathways of lncRNAs in regulating EMT in GC is clarified.
As the leading cause of morbidity and cancer related-death worldwide, pancreatic cancer poses a terrible threat to human health. Since therapeutic choices are limited at the advanced stage, screening and early diagnostic tools are indispensable for a better prognosis. Exosomes are nanovesicles which contain various biomolecules, such as nucleic acids, proteins and lipids. Besides, Exosomes are recognized as potential tools which can be used in tumor diagnosis and therapy, for they are involved in a multitude of pathological and biological processes, mainly for the roles they play in intercellular communication. Here, we will summarize the function of exosomes, mainly in pancreatic cancer (proliferation, metastasis, drug resistance and immune reaction in tumor microenvironment), and importantly, the potential functions of exosomes are also emphasized. Exosomes are not only biomarkers, but they can also work as a tool which is helpful for therapeutic armamentarium in pancreatic cancer. Besides, current challenges which may obstruct the clinical application of exosomes are also discussed in this paper. In-depth researches on the functions of exosomes in pancreatic cancer are still required.
Background: Changes in expression profiles of the 5 selected miRNAs were analysed in a group of PC patients before treatment, after hormonotherapy and radiotherapy. Objective: Whether the expression profiles of the miRNAs may be useful for monitoring prostate cancer treatment. Methods: The initial study was carried out on 44 advanced prostate cancer patients and 41 healthy volunteers. The target group consisted of 39 PC patients. Blood for miRNA analysis was taken before treatment, after hormonotherapy and radiotherapy. The miRNAs were analysed by real-time PCR, followed by statistical analysis. Results: For the target group, the statistically significant differences in the expression level were found after radiotherapy: for miR-21 only in the group of patients above the cut-off value designed in the preliminary study (p=0.0369) and miR-100 for the whole group (p=0.0413) and for the above cut-off value group (p=0.0140). The differences between the levels of each miRNA between the high and low expression groups were statistically significant. The designed groups were stable during treatment. Inclusion to the high and low expression group levels did not influence the treatment result. Conclusion: The miRNAs studied in this work could not serve as biomarkers for the effectiveness of therapy for prostate cancer patients.
