Retroperitoneal Liposarcoma: A Case Report and Review of Literature

Liposarcomas are rare malignant tumours of adipocytic differentiation and are classified under the soft tissue sarcoma subtype histologically. Retroperitoneal liposarcoma (RPL) has an incidence of 1 per 2.5 million individuals, and the retroperitoneum is the second most common site for a liposarcoma, following the lower limb as the most common site. The retroperitoneum is a space that can easily expand; therefore tumours grow in this space without any symptoms until they are very large. This case study reports a patient diagnosed with a retroperitoneal liposarcoma treated with primary radical surgery and the patient is currently being followed-up in our unit with close monitoring and Computed Tomographic (CT) imaging. The patient consented to the reporting of this case.

The effects of locomotion on bone marrow mesenchymal stem cell fate: insight into mechanical regulation and bone formation

Bone marrow mesenchymal stem cells (BMSCs) refer to a heterogeneous population of cells with the capacity for self-renewal. BMSCs have multi-directional differentiation potential and can differentiate into chondrocytes, osteoblasts, and adipocytes under specific microenvironment or mechanical regulation. The activities of BMSCs are closely related to bone quality. Previous studies have shown that BMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. Thus, a goal of this review is to discuss how these ubiquious signals arising from mechanical stimulation are perceived by BMSCs and then how the cells respond to them. Studies in recent years reported a significant effect of locomotion on the migration, proliferation and differentiation of BMSCs, thus, contributing to our bone mass. This regulation is realized by the various intersecting signaling pathways including RhoA/Rock, IFG, BMP and Wnt signalling. The mechanoresponse of BMSCs also provides guidance for maintaining bone health by taking appropriate exercises. This review will summarize the regulatory effects of locomotion/mechanical loading on BMSCs activities. Besides, a number of signalling pathways govern MSC fate towards osteogenic or adipocytic differentiation will be discussed. The understanding of mechanoresponse of BMSCs makes the foundation for translational medicine.

Identification of a clinical signature predictive of differentiation fate of human bone marrow stromal cells

Background Transplantation of human bone marrow stromal cells (hBMSCs) is a promising therapy for bone regeneration due to their ability to differentiate into bone forming osteoblastic cells. However, transplanted hBMSCs exhibit variable capacity for bone formation resulting in inconsistent clinical outcome. The aim of the study was to identify a set of donor- and cell-related characteristics that detect hBMSCs with optimal osteoblastic differentiation capacity. Methods We collected hBMSCs from 58 patients undergoing surgery for bone fracture. Clinical profile of the donors and in vitro characteristics of cultured hBMSCs were included in uni- and multivariable analysis to determine their predictive value for osteoblastic versus adipocytic differentiation capacity assessed by quantification of mineralized matrix and mature adipocyte formation, respectively. Results We identified a signature that explained > 50% of variation in osteoblastic differentiation outcome which included the following positive predictors: donor sex (male), absence of osteoporosis diagnosis, intake of vitamin D supplements, higher fraction of CD146+, and alkaline phosphate (ALP+) cells. With the exception of vitamin D and ALP+ cells, these variables were also negative predictors of adipocytic differentiation. Conclusions Using a combination of clinical and cellular criteria, it is possible to predict differentiation outcome of hBMSCs. This signature may be helpful in selecting donor cells in clinical trials of bone regeneration.

Magnetic resonance imaging assessment of chemotherapy-related adipocytic maturation in myxoid/round cell liposarcomas: specificity and prognostic value

Objective: To investigate the specificity, clinical implication and prognostic value of MRI adipocytic maturation (MAM) in myxoid/round cells liposarcomas (MRC-LPS) treated with neoadjuvant chemotherapy (NAC). Methods: Of the 89 patients diagnosed with MRC-LPS at our sarcoma reference center between 2008 and 2018, 28 were included as they were treated with NAC, surgery and radiotherapy. All patients underwent contrast-enhanced MRIs at baseline and late evaluation. A control cohort of 13 high-grade pleomorphic and dedifferentiated LPS with same inclusion criteria was used to evaluate the specificity of MAM in MRC-LPS. Two radiologists analyzed the occurrence of MAM, changes in the tumor architecture, shape and surrounding tissues during NAC. Pathological features of tumor samples were reviewed and correlated with MRI. Metastatic relapse-free survival was estimated with Kaplan–Meier curves and Cox models. Associations between prognostic T1-based delta-radiomics features and MAM were investigated with Student t-test. Results: MAM was more frequent in MRC-LPS (p = 0.045) and not specific of any type of chemotherapy (p = 0.7). Regarding MRC-LPS, 14 out of 28 patients (50%) demonstrated MAM. Eight patients showed metastatic relapses. MAM was not associated with metastatic relapse-free survival (p = 0.9). MAM correlated strongly with the percentage of histological adipocytic differentiation on surgical specimen (p < 0.001), which still expressed the tumor marker NY-ESO-1. None of the prognostic T1-based delta-radiomics features was associated with MAM. Conclusion: MAM seems a neutral event during NAC. Advances in knowledge: MAM predominated in MRC-LPS and was not specific of a type of chemotherapy. Occurrence of MAM was not associated with better patients’ metastasis free survival.

miR-26b-5p/TCF-4 Controls the Adipogenic Differentiation of Human Adipose-derived Mesenchymal Stem Cells

In this study, we assessed the ability of miR-26b-5p to regulate T cell factor 4 (TCF-4) expression and thereby control human adipose-derived mesenchymal stem cell (hADMSC) adipogenic differentiation. Adipogenic medium was used to induce hADMSC differentiation over a 6-d period. The ability of miR-26b-5p to interact with the TCF-4 mRNA was confirmed through both predictive bioinformatics analyses and luciferase reporter assays. Immunofluorescent staining was used to visualize the impact of miR-26b-5p inhibition or overexpression on TCF-4 and β-catenin levels in hADMSCs. Further functional analyses were conducted by transfecting these cells with siRNAs specific for TCF-4 and β-catenin. Adipogenic marker and Wnt/β-catenin pathway gene expression levels were assessed via real-time polymerase chain reaction and western blotting. β-catenin localization was assessed via immunofluorescent staining. As expected, our adipogenic media induced the adipocytic differentiation of hADMSCs. In addition, we confirmed that TCF-4 is an miR-26b-5p target gene in these cells, and that protein levels of both TCF-4 and β-catenin were reduced when these cells were transfected with miR-26b-5p mimics. Overexpression of this microRNA also enhanced hADMSC adipogenesis, whereas TCF-4 and β-catenin overexpression inhibited this process. The enhanced hADMSC adipogenic differentiation that was observed following TCF-4 or β-catenin knockdown was partially reversed when miR-26b-5p expression was inhibited. We found that miR-26b-5p serves as a direct negative regulator of TCF-4 expression within hADMSCs, leading to inactivation of the Wnt/β-catenin pathway and thereby promoting the adipogenic differentiation of these cells in vitro.