Expression of the preadipocyte marker ZFP423 is dysregulated between well-differentiated and dedifferentiated liposarcoma.

BACKGROUND: Well-differentiated and dedifferentiated liposarcomas are rare soft tissue tumors originating in adipose tissue that share genetic abnormalities but have significantly different metastatic potential. Dedifferentiated liposarcoma (DDLPS) is highly aggressive and has an overall 5-year survival rate of 30% as compared to 90% for well-differentiated liposarcoma (WDLPS). This discrepancy may be connected to their potential to form adipocytes, where WDLPS is adipogenic but DDLPS is adipogenic-impaired. Normal adipogenesis requires Zinc Finger Protein 423 (ZFP423), a transcriptional coregulator of Perixosome Proliferator Activated Receptor gamma (PPARG2) mRNA expression that defines committed preadipocytes. Expression of ZFP423 in preadipocytes is promoted by Seven-In-Absentia Homolog 2 (SIAH2)-mediated degradation of Zinc Finger Protein 521 (ZFP521). This study investigated the potential role of ZFP423, SIAH2 and ZFP521 in the adipogenic potential of WDLPS and DDLPS. METHODS: Human WDLPS and DDLPS fresh and paraffin-embedded tissues were used to assess the gene and protein expression of proadipogenic regulators. In parallel, normal adipose tissue stromal cells along with WDLPS and DDLPS cell lines were cultured, genetically modified, and induced to undergo adipogenesis in vitro. RESULTS: Impaired adipogenic potential in DDLPS was associated with reduced ZFP423 protein levels in parallel with reduced PPARG2 expression, potentially involving regulation of ZFP521. SIAH2 protein levels did not define a clear distinction related to adipogenesis in these liposarcomas. However, in primary tumor specimens, SIAH2 mRNA was consistently upregulated in DDLPS compared to WDLPS when assayed by fluorescence in situ hybridization or real-time PCR. CONCLUSIONS: These data provide novel insights into ZFP423 expression in adipogenic regulation between WDLPS and DDLPS adipocytic tumor development. The data also introduces SIAH2 mRNA levels as a possible molecular marker to distinguish between WDLPS and DDLPS.

Treatment of a recurrent ischial ulcer with injected exosomes.

Pressure ulcers (PUs) affect 2.5 million patients per year. Even after successful reconstruction, 50% of PUs recur. Patients with multiply recurrent PUs eventually consume all locoregional donor sites. This underscores the need for novel, less invasive approaches in PU reconstruction. Here, we report the first successful use of mesenchymal stem cell exosomes in PU reconstruction. The patient presented with a right ischial ulcer that persisted despite 9 months of wound care and appropriate antibiotic therapy. After six subcutaneous ExoFlo exosome injections over 8 weeks, the PU was completely healed. Additional studies of this promising technology should be performed.

Reconstruction of Bilateral Mandibular Condyles Using a Single Vascularized Fibula.

Patients with end-stage temporomandibular joint (TMJ) pathology present with loss of vertical ramus height with resulting retrognathia, anterior open bite, and restricted jaw function requiring joint reconstruction. Costochondral grafts, long considered the gold standard for TMJ reconstruction, carry risks of bony ankylosis and resorption. Custom-made alloplastic TMJ prostheses show excellent objective and subjective outcomes but are also associated with complications such as infection or metal sensitivity, and necessitate hardware explantation in some cases. Revision surgeries are rare but present a real challenge. We present the case of a 50-year-old woman with longstanding TMJ arthritis, having undergone many surgical procedures to her TMJ, including explantation of failed alloplastic replacement, who presented with bilateral facial weakness as well as difficulty chewing and swallowing food. She had class II malocclusion with retrodisplacement of her mandible and anterior open bite, and moderate trismus with an inter-incisal opening of only 15 mm, consistent with fibrous ankylosis. After weighing all the reconstructive options, bilateral mandibular condyle and ramus reconstruction with a single fibula free flap (FFF) was planned with the use of preoperative virtual surgical planning (VSP) and 3D-printing of osteotomy and repositioning guides. A 2-team approach increases efficiency of the procedure and decreases operative time. The procedure and postoperative recovery were uncomplicated, and at her 2-month follow-up, she had increased range of motion and maintained the planned position of her mandible. Her masticatory function and deglutition were also improved due to the correction of her malocclusion and repair of her anterior open bite.