Angiogenic cells, macroparticles and RNA transcripts in laparoscopic vs open surgery for colorectal cancer

Angiogenesis is crucial for tissue repair and cancer progression. We investigated a panel of angiogenic cells, macroparticles and RNA transcripts before, during and after laparoscopic colectomy or open colectomy for colorectal cancer

Circulating endothelial progenitors are increased in Covid‐19 patients and correlate with SARS‐CoV‐2 RNA in severe cases

Background During the course of COVID-19, the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thrombotic phenomena and/or diffuse vascular damage are frequent, and viral elements have been observed within endothelial cells. Objectives CD146 + circulating endothelial cells (CD146 + CECs) and their progenitors (CEPs) are increased in cardiovascular, thrombotic, infectious, and cancer diseases. The present study was designed to investigate their kinetics in novel coronavirus (COVID-19) patients. Methods We used a validated flow cytometry procedure to enumerate viable and apoptotic CD146 + CECs and CEPs in COVID-19 patients during the course of the disease and in patients who recovered. Results Viable CEPs per milliliter were significantly increased in COVID-19 patients compared with healthy controls. This increase was observed in patients with mild symptoms and not further augmented in patients with severe symptoms. In patients who recovered, CEPs decreased, but were in a range still significantly higher than normal controls. Regarding mature CD146 + CECs, in COVID-19 patients, their absolute number was similar to those observed in healthy controls, but the viable/apoptotic CD146 + CEC ratio was significantly different. Both mild and severe COVID-19 patients had significantly less apoptotic CD146 + CECs compared with healthy controls. Patients who recovered had significantly less CD146 + CECs per milliliter when compared with controls as well as to mild and severe COVID-19 patients. A positive correlation was found between the copies of SARS-CoV-2 RNA in the cellular fraction and apoptotic CEPs per milliliter in severe COVID-19 patients. Conclusions CD146 + CECs and CEPs might be investigated as candidate biomarkers of endothelial damage in COVID-19 patients

Optimized glycaemic control achieved with add-on basal insulin therapy improves indexes of endothelial damage and regeneration in type 2 diabetic patients with macroangiopathy: a randomized crossover trial comparing detemir versus glargine.

AIMS: In diabetes, endothelial damage promotes macroangiopathy and endothelial regeneration is impaired, owing to reduced endothelial progenitor cells (EPCs). Given that insulin influences endothelial biology, we compared the effects of add-on basal insulin analogues on endothelial damage and regeneration in type 2 diabetes (T2D). METHODS: This was a 6-month randomized crossover trial comparing add-on insulin detemir versus glargine in poorly controlled T2D with macroangiopathy. At baseline, crossover (3 months) and study end (6 months), we measured HbA1c, EPCs, circulating endothelial cells (CECs), VCAM-1, ICAM-1 and E-selectin. Body weight and hypoglycaemic episodes were also recorded. RESULTS: Forty-two patients completed the study, randomly assigned to the glargine-detemir (n = 21) or the detemir-glargine (n = 21) schedule. At crossover, EPC levels did not change compared with baseline, but significantly increased at study end. CECs decreased over time and were significantly reduced at study end. ICAM-1, VCAM-1 and E-selectin were significantly reduced at crossover and further decreased at study end. No differences were seen in these effects between detemir and glargine. HbA1c showed a carryover effect and its reduction was similar with detemir and glargine in the first arm. Incidence of hypoglycaemia and weight gain was lower with detemir than with glargine in both arms. CONCLUSION: Optimized glycaemic control by add-on basal insulin improved indexes of endothelial damage and regeneration. Compared to glargine, detemir achieved similar endothelial protection with lower weight gain and less hypoglycaemia. These results might have implications for therapy of aging T2D patients with cardiovascular disease

Validation of a standardized method for enumerating circulating endothelial cells and progenitors: flow cytometry and molecular and ultrastructural analyses

Purpose: Antigenic overlap among circulating endothelial cells (CEC) and progenitors (CEP), platelets, and other blood cells led to the need to develop a reliable standardized method for CEC and CEP quantification. These cells are emerging as promising preclinical/clinical tools to define optimal biological doses of antiangiogenic therapies and to help stratify patients in clinical trials. Experimental Design: We report the experimental validation of a novel flow cytometry method that precisely dissects CEC/CEP from platelets and other cell populations and provides information about CEC/CEP viability. Results: Sorted DNA/Syto16 +CD45 -CD31 +CD146 + CECs, investigated by electron microscopy, were found to be bona fide endothelial cells by the presence of Weibel-Palade bodies. More than 75% of the circulating mRNAs of the endothelial-specific gene, VE-cadherin, found in the blood were present in the sorted population. CECs were 140 \ub1 171/mL in healthy subjects (n = 37) and 951 \ub1 1,876/mL in cancer patients (n - 78; P \uab 0.0001). The fraction of apoptotic/necrotic CECs was 77 \ub1 14% in healthy subjects and 43 \ub1 23% in cancer patients (P \uab 0.0001). CEPs were 181 \ub1 167/mL in healthy donors and 429 \ub1 507/mL in patients (P = 0.00019). Coefficients of variation were 4 \ub1 4% (intrareader), 17 \ub1 4% (interreader), and 17 \ub1 7% (variability over 0-72 h), respectively. Parallel samples were frozen by a standardized protocol. After thawing, coefficients of variation were 12 \ub1 8% (intrareader), 16 \ub1 10% (interreader), and 26 \ub1 16% (variability over 0-14 days of frozen storage), respectively. Conclusions: This procedure enumerates a truly endothelial cell population with limited intrareader and interreader variability. It appears possible to freeze samples for large-scale CEC enumeration during clinical trials. This approach could be enlarged to investigate other angiogenic cell populations as well

Incidence and prognostic significance of karyotype abnormalities in de novo primari myelodysplastic syndromes: a study on 331 patients from a single institution.

The impact of clinical parameters, International Prognostic Scoring System (IPSS) scores/cytogenetic categories, and some single cytogenetic defects on overall survival (OS) and time to myelodysplastic syndromes (MDS)/AML progression (progression-free interval (PFI)) was evaluated in 331 MDS patients. Statistical analysis demonstrated that OS and PFI were significantly affected by all these parameters. Since single 7q- showed a better survival than the poor IPSS cytogenetic category (P=0.009), it was considered as a new prognostic entity ('modified IPSS categories'). In multivariate analysis OS was significantly influenced by age, marrow blast cell percentage, number of cytopenias and either modified or standard IPSS cytogenetic categories; hazard ratios for MDS/AML progression were influenced by all the former, except for age and cytopenias. Multivariate analysis of del(7)(q31q35) confirmed the results of univariate analysis, but the Akaike Information Criterion showed no difference in evaluating OS and PFI between the modified and standard IPSS cytogenetic grouping. In conclusion, (i) chromosome defects as grouped by IPSS and blast cell percentage are the most relevant parameters for predicting OS and PFI; (ii) the prognostic power of the IPSS cytogenetic grouping is not ameliorated by the introduction of del(7)(q31q35) as a new entity; (iii) complex karyotypes have a prognostic value independent of blast cell percentage

Complementary populations of human adipose CD34+ progenitor cells promote growth, angiogenesis, and metastasis of breast cancer

Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer.Wefound that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45CD34\ufeCD31\ufeCD13CCRL2\ufe endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45CD34\ufeCD31CD13\ufeCD140b\ufe mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer