The role of selected molecular factors in ovarian cancer metastasis

The main reason for treatment failure in ovarian cancer is chemoresistance and the presence of metastasis. Ascites, which allows the physical movement of cancer cells, the lymphovascular pathway, and several molecular factors and signalling axes, are involved in metastasis. Ascites, with the involvement of cytokines and chemokines, MAPK/STAT1 and NOTCH as well as CXCL12/CXCR4 signaling pathways and circulating anoikis induces cancer dissemination, in particular to the peritoneum and omentum. The spread of lymphatic and bloodstream cancer cells is a multi-stage process. Tumour infiltration of the stroma and lymphovascular space (LVSI) produces biologically active cancer-associated fibroblasts and macrophages (CAFs, TAMs) that secrete numerous cytokines, chemokines and growth factors, inhibit NK function, induce epithelial-mesenchymal transition (EMT), resulting in an increase of the metastatic potential of cancer cells and the formation of cancer stem cells (CSCs). Overexpression of some genes, and microRNAs, in LVSI-(LMGS) associated with metastasis has been identified. The role of extracellular vesicles (EVs) transporting metastasis-associated factors has been described as has the role of cancer stem cells (CSCs) in chemotherapy resistance and metastasis. Sirtuins, enzymes involved in metastasis formation, have also been detected. Certain types of microRNAs (miR-509-3p, microRNA-506-3p) and melatonin have been shown to inhibit metastasis.  

The Estimation of GC Repeats in Promoter P1 of IGF-1 Gene and Their Influence on IGF-1 Plasma Levels in Stable Angina Patients

Increased plasma levels of insulin-like growth factor 1 (IGF-1) are observed in advanced arteriosclerosis, but the reasons for these elevated levels remain unknown. One possibility to explain them is variation in the sequences that control IGF-1 gene expression. The goal of this study was to determine the effect of molecular variants of the IGF-1 P1 promoter on IGF-1 serum levels and to determine the impact of IGF-1 levels on the severity of coronary atherosclerosis. Methods: Blood samples were collected from 101 consecutive patients undergoing routine angiography. Genomic DNA was isolated from the nucleated cells of the blood plasma as described (2). Based on the presence of conformational differences in the DNA strand and on the absence of single nucleotide polymorphisms, the DNA from 38 patients was further analyzed by the “allelic ladder” method to determine the number of repeated GC dinucleotides in the P1 promoter of the IGF-1 gene. In addition, we analyzed serum growth hormone levels in order to examine the effect on systemic IGF-1 synthesis. Results: Conformational differences in the P1 promoter of the IGF-1 gene were observed in 38 out of the 101 patients. Several genotypes, depending on the number of GC repeats, were observed (11/19,17/19,18/19,18/21,19/19,19/20,19/21). Interestingly, a family history of coronary artery disease was seen less often among individuals heterozygous for the GC repeats. A lower IGF-1 levels were seen in non-variant carriers (homozygous genotypes for 19 or 21 repeats of GC, or heterozygous genotype 19/21) when compared to the variant group (other heterozygous genotypes then 19/21) (181.6 ± 47.9 ng/mL vs. 227.7 ± 73.7, p = 0.026). A correlation between IGF-1, IGF-binding protein number 3, and growth hormone levels (p = ns) was not observed, and there were no significant differences in the growth hormone levels in the studied group of patients (p = ns)

Are Elevated Levels of IGF-1 Caused by Coronary Arteriesoclerosis?: Molecular and Clinical Analysis

The importance of insulin-like growth factor-1 (IGF-1) in coronary artery disease (CAD) due to wide range of its biological effects and its therapeutic potential, has already been described. Our aim was to evaluate possible influence of IGF-1 serum level changes on coronary atherosclerosis. In case of existence of such association our further aim was to verify and explain this phenomenon by examination of promoter P1 of IGF-1gene and receptor gene for IGF-1. The study was performed in 101 consecutive patients undergo for routine coronary angiography. Quantitative and qualitative assessment of coronary atherosclerosis was performed respectively by estimation of the number of culprit lesions in coronary arteries and by Gensini score calculation. IGF-1, IGFBP3 and plasma lipoproteins were measured in all patients. In addition, we evaluated DNA from 101 patients, isolated from blood cells, which was amplified by using PCR with sophisticated primers for P1 promoter of IGF-1 gene and IGF-1 receptor gene, then analyzed utilizing SSCP technique and automatically sequenced. We observed significant increase of serum IGF-1 levels in patients with “3 vessel disease” and with high score in Gensini scale when compared to those without any narrowing lesions in coronary arteries and 0 Gensini score (in group with 3 vessel disease 215.0 ± 71.3 versuss 176.7 ± 34.2 ng/ml p = 0.04 and with high Gensini score 231.4 ± 59.3 versus 181.0 ± 37.8 ng/ml p = 0.01).We found different genotypes for five P1 promoter polymorphisms of IGF-1 gene (RS35767, RS5742612, RS228837, RS11829693, RS17879774). There were no significant associations between the observed single nucleotide polymorphism (SNP) and coronary atherosclerosis nor with levels of circulating IGF-1. We found no structural polymorphism in receptor gene for IGF-1 nor in its extracellular domain(exon 2–4) nor in internal domain (exon 16–21). The effect of increased IGF-1 serum level in our study was probably independent from structural polymorphism in promoter P1 for IGF-1 or in receptor gene for IGF-1

Lack of Serum Creatinine Decrease After Coronary Angiography Despite Prophylactic Hydration After Routine Coronary Angiography/Angioplasty in Stable Angina Patients - Pilot Study

Background/Aims: To prevent contrast induced renal dysfunction a periprocedural prophylactic hydration is applied. Due to dilution it should cause a drop in serum creatinine concentration (SCR). Surprisingly, no reduction in SCR after contrast admission is found in up to 25% of patients as early as 12-18 hours after coronary angiography/angioplasty. This study aims to find a clinical explanation as well as predict circumstances for this phenomenon. Methods: Retrospective clinical and laboratory data was used from 341 patients who underwent elective coronary angiography/angioplasty, received a prophylactic hydration, and had serum creatinine concentration measured prior to, and 12-18 hours after invasive procedure with iodine contrast administration. To exclude an improper hydration due to no creatinine decrease, the number of red blood cells was analysed as well as hemoglobin and hematocrit in blood donations collected during the study time points. Results: The resulting lack of serum creatinine reduction could be explained by dehydration (measured by increase in number of RBC, HGB and HCT) only in 13.5% , 10.8 %, and 20% of cases, respectively. Any form of abnormal glucose metabolism combined with either baseline serum creatinine concentration 86.77 mL/min, or GFR by CKD EPI >80.08 mL/min/1.73 m2, or GFR by MDRD >74.48 mL/min/1.73 m2 were the predictors for no creatinine decrease at outcome. Additionally, it was demonstrated that the lack of creatinine decrease was more often observed among those patients whose initial renal function was better than in the subjects with reduction of SCR. Conclusions: This observation requires further prospective investigation on extended group of patients

Formation and Properties of Biomedical Ti-Ta Foams Prepared from Nanoprecursors by Thermal Dealloying Process

The paper presents a promising method of preparation of titanium-based foams by the thermal dealloying method. The first step of this study was the Ti-Ta-Mg based nanopowder preparation using the mechanical alloying (MA) process performed at room temperature. The next step was forming the green compacts by cold pressing and then sintering with magnesium dealloying from the titanium-based alloy structure. The mechanism of the porous structure formation was based on the removal of magnesium from the titanium alloy at a temperature higher than the boiling point of magnesium (1090 °C). The influence of the Mg content on the formation of the porous Ti-30Ta foam has been investigated. The sintering stage was performed in vacuum. During the dealloying process, the magnesium atoms diffuse from the middle to the surface of the sample and combine to form vapors and then evaporate leaving pores surrounded by the metallic scaffold. The porosity, the mechanical properties as well as biocompatibility have been investigated. The titanium-based foam of high porosity (up to 76%) and the pore size distribution from nano- to micro-scale have been successfully prepared. For the medical applications, the Ti-Ta metallic foams have shown a positive behavior in the MTT test. The as-shown results clearly exhibit a great potential for thermal dealloying in the preparation of porous structures