Prognostic significance of prognostic nutritional index and systemic immune-inflammation index in patients after curative breast cancer resection: a retrospective cohort study.

BACKGROUND: Nutritional status and inflammation are closely associated with poor outcome in malignant tumors. However, the prognostic impact of postoperative in these variables on breast cancer (BC) remains inconclusive. We aimed to determine whether prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) affect two long-term outcomes among patients after curative resection of BC. METHODS: We retrospectively reviewed 508 patients with BC treated with curative surgery between February 5, 2013 and May 26, 2020. All patients were divided into 3 groups based on tertiles (T1-T3) of PNI, SII, NLR, and PLR. The effects of four indexes on disease-free survival (DFS) and overall survival (OS) have been evaluated using Cox proportional hazards models and Kaplan-Meier method. RESULTS: Compared with PNI-lowest cases, patients with highest PNI showed significantly longer DFS (multivariate adjusted hazard ratio [HR] = 0.37, 95% confident interval [CI] 0.19-0.70, P for trend = 0.002), whereas higher PLR seemed to be marginally associated with poorer DFS (P for trend = 0.086 and 0.074, respectively). Subgroup analyses indicate the potential modification effects of family history of BC and radiotherapy on the prognosis value of PNI to DFS in BC patients (P for interaction = 0.004 and 0.025, respectively). In addition, the levels of three inflammatory indices, namely SII, NLR, and PLR might be positively related with increased age at diagnosis (all P for trend < 0.001). CONCLUSIONS: A high PNI was associated with better DFS, supporting its roles as prognostic parameters for patients with BC. The nutritional status and systemic immune may exert great effects on patient prognosis. Further studies are warrant to explore the prognosis value of PLR.

GM-CSF accelerates proliferation of endothelial progenitor cells from murine bone marrow mononuclear cells in vitro.

OBJECTIVE: To test whether the GM-CSF accelerates the proliferation of bone marrow endothelial progenitor cells (BM EPCs). METHODS: BM EPCs were induced by endothelial cell conditioned medium (EC-CM). The effect of different concentrations of GM-CSF on the proliferation of BM EPCs was evaluated by the formation of EC-cols, MTT assay, and cell cycle assay. The single progenitor cell growth curves were quantified. RESULTS: The data indicated that GM-CSF accelerated the proliferation of BM EPCs both in colony numbers and colony size. MTT confirmed the effect of GM-CSF on accelerating the proliferation of BM EPCs. The single colony experiments showed that EC-cols expressed different proliferation capacity, suggesting that the EC-cols with different proliferation potentials might have been derived from different levels of immature progenitors. The cell cycle assay showed that the rate of cells entering into S phase was 9.3% in the group treated with GM-CSF and 2.1% in the controls. Furthermore, these cells displayed the specific endothelial cell markers and formed capillary-like structures. CONCLUSIONS: GM-CSF accelerates proliferation of BM EPCs. The potential beneficial of GM-CSF in the application of treating vascular ischemic patients is promising.

Retrospective analysis of the utility of multiparametric MRI for differentiating between benign and malignant breast lesions in women in China.

We explored the utility of time-resolved angiography with interleaved stochastic trajectories dynamic contrast-enhanced magnetic resonance imaging (TWIST DCE-MRI), readout segmentation of long variable echo-trains diffusion-weighted magnetic resonance imaging- diffusion-weighted magnetic resonance imaging (RESOLVE-DWI), and echo-planar imaging- diffusion-weighted magnetic resonance imaging (EPI-DWI) for distinguishing between malignant and benign breast lesions.This retrospective analysis included female patients with breast lesions seen at a single center in China between January 2016 and April 2016. Patients were allocated to a benign or malignant group based on pathologic diagnosis. All patients received routine MRI, RESOLVE-DWI, EPI-DWI, and TWIST DCE-T1WI. Variables measured included quantitative parameters (K, Kep, and Ve), semiquantitative parameters (rate of contrast enhancement for contrast agent inflow [W-in], rate of contrast decay for contrast agent outflow [W-out], and time-to-peak enhancement after contrast agent injection [TTP]) and apparent diffusion coefficient (ADC) values for RESOLVE-DWI (ADCr) and EPI-DWI (ADCe). Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic utility of each parameter for differentiating malignant from benign breast lesions.A total of 87 patients were included (benign, n = 20; malignant, n = 67). Compared with the benign group, the malignant group had significantly higher K, Kep and W-in and significantly lower W-out, TTP, ADCe, and ADCr (all P < .05); Ve was not significantly different between groups. RESOLVE-DWI was superior to conventional EPI-DWI at illustrating lesion boundary and morphology, while ADCr was significantly lower than ADCe in all patients. Kep, W-out, ADCr, and ADCe showed the highest diagnostic efficiency (based on AUC value) for differentiating between benign and malignant lesions. Combining 3 parameters (Kep, W-out, and ADCr) had a higher diagnostic efficiency (AUC, 0.965) than any individual parameter and distinguished between benign and malignant lesions with high sensitivity (91.0%), specificity (95.0%), and accuracy (91.9%).An index combining Kep, W-out, and ADCr could potentially be used for the differential diagnosis of breast lesions.

An in vitro study of differentiation of hematopoietic cells to endothelial cells.

Bone-marrow-derived endothelial progenitor cells (BM-EPCs) contribute to postnatal neovascularization and therefore are of great interest for cell therapies to treat ischemic diseases. However, their origin and characteristics are still in controversy. In this paper, we identified the origin/lineage of the BM-EPCs that were isolated from bone marrow mononuclear cells and differentiated with the induction of bone-marrow endothelial-cellconditioned medium (ECCM). BM-EPCs were characterized in terms of phenotype, lineage potential, and their functional properties. Endothelial cell colonies derived from BM-EPC were cultured with ECCM for 3 months. Cultured EPC colony cells expressed endothelial cell markers and formed the capillary-like network in vitro. EPC colony cells expressed differential proliferative capacity; some of the colonies exhibited a high proliferative potential (HPP) capacity up to 20 population doublings. More importantly, these HPP-EPCs expressed hematopoietic marker CD45, exhibited endocytic activities, and preserved some of the myeloid cell activity. In addition, the HPP-EPCs secrete various growth factors including VEGF and GM-CSF into the culture medium. The results demonstrate that these EPCs were primarily derived from hematopoietic origin of early precursor cells and maintained high proliferative potential capacity, a feature with a significant potential in the application of cell therapy in ischemic diseases.

[Cultivation and purification of high proliferative potential endothelial progenitor cells from murine bone marrow].

The present study was designed to culture and purify high proliferative potential endothelial progenitor cells (HPP-EPCs) from murine bone marrow and their progeny cells using a culture system which has been established by us recently, in order for more intensive researches on these cells. Fresh murine bone marrow cells were preplated to allow the preferential attachment of non-EPCs to tissue culture plates and then unattached cells were repreplated in the culture system containing the bone marrow endothelial cell line-conditioned medium (BMEC-CM). The colonies containing about 2 x 10(4) cells were collected respectively and single colony-derived cells were cultured for their expansion in the above-mentioned culture system. These single colonies were able to yield 8 x 10(6) progeny cells. The endothelial-lineage characteristics of expanded cells were confirmed by immunofluorescent staining for CD31 and vWF, FITC-UEA-1 binding and Dil-Ac-LDL uptake. These data suggest that murine bone marrow HPP-EPCs can proliferate exuberantly so that their progeny cells can be obtained with high yield by using the single colony-derived cell culture in the presence of BMEC-CM.

[Long-term subculture and biological characterization of the murine bone marrow endothelial cell line].

The murine bone marrow endothelial cell line (mBMEC) has been maintained by means of subculture and cryopreservation for over 10 years since it was established in our laboratory. This study was aimed to newly identify biological characteristics of this cell line for further study. The cultured mBMEC cells were observed by inverted microscopy and transmission electron microscopy (TEM). PECAM-1 (CD31) and von Willebrand factor (vWF) were detected by immunofluorescent staining. The phagocytotic activity of the cells in culture was tested by using fluorescent acetylated low-density lipoprotein (Dil-Ac-LDL). The cell growth kinetics analysis and karyotype analysis were performed. The results showed that the adherent cells were mostly elliptical, rounded and spindle-shaped, and some of them connected to each other to form cord- and network-like arrangements in mBMEC cultures at subconfluence. The adherent cells grew up to confluence as a cobblestone-like monolayer. Several ultrastructural features of the endothelial cells could be observed in TEM sections of the cultured cells. More than 94% of mBMEC cells were positive for either CD31 or vWF. The phagocytotic ingestion of Dil-Ac-LDL occurred in 98.5% of cells. In normal culture conditions, the cells grew with a mean population doubling time of 54.6 hours and the maximal mitotic index was 38 per thousand in the rapid growth period. The colony yields were 4.33% to 7.40% depending on the plating density of cells. Karyotypes of all the cells were aneuploidy with a greater percentage of hyperdiploid. It is concluded that mBMEC cells retain the fundamental properties of endothelial cells, but the growth kinetics and biological behaviors are slightly different from those in the early days after the establishment of this cell line.