Differentiation between adenocarcinomas is sometimes challenging. The promising avenue for discovering new biomarkers lies in bioinformatics using DNA methylation analysis. Utilizing a 2853-sample ...identification dataset and a 782-sample independent verification dataset, we have identified diagnostic DNA methylation biomarkers that are hypermethylated in cancer and differentiate between breast invasive carcinoma, cholangiocarcinoma, colorectal cancer, hepatocellular carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma and stomach adenocarcinoma. The best panels for cancer type exhibit sensitivity of 77.8-95.9%, a specificity of 92.7-97.5% for tumors, a specificity of 91.5-97.7% for tumors and normal tissues and a diagnostic accuracy of 85.3-96.4%. We have shown that the results can be extended from the primary cancers to their liver metastases, as the best panels diagnose and differentiate between pancreatic adenocarcinoma liver metastases and breast invasive carcinoma liver metastases with a sensitivity and specificity of 83.3-100% and a diagnostic accuracy of 86.8-91.9%. Moreover, the panels could detect hypermethylation of selected regions in the cell-free DNA of patients with liver metastases. At the same time, these were unmethylated in the cell-free DNA of healthy donors, confirming their applicability for liquid biopsies.
Malignant liver tumors include primary malignant liver tumors and liver metastases. They are among the most common malignancies worldwide. The disease has a poor prognosis and poor overall survival, ...especially with liver metastases. Therefore, early detection and differentiation between malignant liver tumors are critical for patient treatment selection. The detection of cancer and the prediction of its origin is possible with a DNA methylation profile of the tumor DNA compared to that of normal cells, which reflects tissue differentiation and malignant transformation. New technologies enable the characterization of the tumor methylome in circulating tumor DNA (ctDNA), providing a variety of new ctDNA methylation biomarkers, which can provide additional information to clinical decision-making. Our review of the literature provides insight into methylation changes in ctDNA from patients with common malignant liver tumors and can serve as a starting point for further research.
Cell-flee DNA （cfDNA） is small short double stranded molecule that is also found in seminal fluid. It is a product ofapoptotic cells in different developmental stages during spermatogenesis. To final ...concentration of total cfDNA in semen contributesalso cfDNA secreted from living cells and cfDNA that is result of different diseases e.g. prostate cancer or infertility. Amendedconcentration （high or low） can be connected to prostate cancer or male infertility and can represent important non-invasive diagnosticbiomarker for detection and prognosis of these pathological conditions. In this paper, I will discuss different approaches for isolation ofcfDNA from seminal fluid, which includes selection of the samples, separation, isolation, extraction, purification and analysis. Today＇smost popular approach for isolation is the use of commercial kits based on selective binding and elution on silica-membrane technology,magnetic-bead technology or extraction with organic solvents and salting out procedure. Furthermore I will present that I tried to isolatecfDNA from semen with QIAamp DNA Mini Kit to confirm the presence of cell-free DNA in our samples. In the end I will describeproblems we are facing during cfDNA measurement which are mainly associated with low concentration of cfDNA in samples.
Reaction of CuX2 salts (X = NO3− and CF3SO3−) with 4,7-phenanthroline leads to the formation of Cu(NO3)2(4,7-Hphen)2(NO3)2 and Cu(CF3SO3)(4,7-phen)2(H2O)2CF3SO3 complexes, while with ...1,7-phenanthroline, only 1,7-HphenNO3 and 1,7-HphenCF3SO3 salts were formed as the final reaction products.
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The reactions between equimolar amounts of CuX2 (X = NO3− and CF3SO3−) and two aromatic nitrogen-containing heterocycles differing in the position of nitrogen atoms, 1,7- and 4,7-phenanthroline (1,7- and 4,7-phen), were performed in ethanol/methanol at room temperature. When CuX2 salts were mixed with 4,7-phen, two copper(II) complexes, Cu(NO3)2(4,7-Hphen)2(NO3)2 (1) and Cu(CF3SO3)(4,7-phen)2(H2O)2CF3SO3 (2), were formed. On the other hand, in the reaction of CuX2 salts with 1,7-phen, only 1,7-HphenNO3 (3a/b) and 1,7-HphenCF3SO3 (4) were obtained as the final products. The obtained products 1–4 were characterized by spectroscopic and X-ray diffraction techniques. In the copper(II) complexes 1 and 2, the coordination geometry around the Cu(II) ion is distorted octahedral and square pyramidal, respectively. The antimicrobial potential of the copper(II) complexes 1 and 2 and corresponding compounds used for their synthesis were assessed against four different bacterial species and Candida albicans, displaying moderate growth inhibiting activity. The cytotoxic properties of the investigated complexes were also evaluated against the normal human lung fibroblast cell line (MRC-5) indicating moderate, yet more pronounced cytotoxicity than antimicrobial properties.
An immune-mediated, severe, acquired prothrombotic disorder, heparin-induced thrombocytopenia type II (HIT II) occurs in 0.5-5% of patients exposed to unfractionated heparin longer than 5-7 days. ...Arterial and venous thromboses are induced by HIT II in about 35-50% of patients. Typical death rate for HIT is about 29%, while 21% of HIT patients result in amputation of a limb. The trend towards the occurrence of HIT due to the administration of low molecular weight heparins (LMWH) taking ever conspicuous place in the standard venous thromboembolism (VTE) prophylaxis has been more frequently observed recently. It is considered that LMWH may cause HIT II in about 0.25-1%. The need for further modification of HIPA assays with LMWH has been imposed in the HIT laboratory diagnostics, heretofore overburdened with complexity. There are several constantly opposing problems arising in HIT laboratory diagnostics, one of which is that in a certain number of patients immunologic assays detect nonpathogenic antibodies (mainly IgM or IgA heparin-PF4 antibodies) while, on the other hand, the occurrence of HIT pathogenetically mediated by minor antigens (neutrophil-activating peptide 2 or interleukin 8) may be neglected in certain cases. The following factors play an important role in the interpretation of each laboratory HIT assays performed: 1. correlation with HIT clinical probability test, the best known of which is 4T'score, 2. the interpretation of the laboratory findings dependent on the time of the thrombocytopenia onset, as well as 3. the sensitivity and specificity of each test respectively. The HIT diagnostics in the presence of other comorbid states which may also induce thrombocytopenia, more precisely known as pseudo HIT (cancer, sepsis, disseminated intravascular coagulation, pulmonary embolism, antiphospholipid syndrome, etc), represents a specific clinical problem.
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