IL-13RA2 downregulation in fibroblasts promotes keloid fibrosis via JAK/STAT6 activation.

Keloids are considered the manifestation of a fibroproliferative disease characterized by chronic inflammation that is induced following skin injury. Deciphering the underlying mechanism of keloid formation is essential for improving treatment outcomes. Here, we found that more macrophages were activated toward the M2 subtype in keloid dermis when compared with normal dermis. Western blotting revealed that the level of phosphorylated STAT6 (p-STAT6), a known inducer of M2 polarization, was higher in keloid fibroblasts as opposed to fibroblasts from normal dermis. Moreover, keloid fibrosis was shown to be positively correlated with the level of p-STAT6. Further, we identified downregulation of IL-13RA2, a decoy receptor for IL-13, in keloid fibroblasts compared with fibroblasts from normal dermis. Ectopic expression of IL-13RA2 in keloid fibroblasts resulted in inhibition of STAT6 phosphorylation, cell proliferation, migration, invasion, extracellular matrix secretion, and myofibroblast marker expression, as well as an increase in apoptosis. Consistently, knockdown of IL-13RA2 in normal fibroblasts induced a keloidal status. Furthermore, both in vitro application and intratumoral injection of p-STAT6 inhibitor AS1517499 in a patient-derived xenograft keloid-implantation mouse model resulted in proliferation inhibition and tissue necrosis, apoptosis, and myofibroblast marker reduction. Collectively, this study elucidates the key role of IL-13RA2 in keloid pathology and inspires further translational research of keloid treatment concerning JAK/STAT6 inhibition.

Clear cell sarcoma of the kidney in an adult: a case report and literature review.

Clear cell sarcoma of the kidney (CCSK) in adults is extremely rare. In fact, only 16 adult CCSK cases have been reported from 1989 to 2020 in the English language literature. The pathologic diagnosis of the disease is difficult, and the optimal treatment is still unknown. Currently, no literature review has been done on adult CCSK patients. Herein, we report the case of a 24-year-old man who presented with right flank pain for one month. The patient underwent a series of diagnostic tests, and imaging examinations revealed a large mass in his right kidney. The patient underwent retroperitoneal laparoscopic nephrectomy and regional lymphadenectomy. Pathological examination of the tumor revealed nests and cords of fairly uniform oval cells with clear cytoplasm. Immunohistochemistry showed that the tumor cells were positive for vimentin, CyclinD1, and Bcl-2 and that the sample was uniformly negative for Wilms' tumor 1 (WT1), CD34, desmin, and cytokeratin staining. Based on these histopathological and immunohistochemical results, the patient was diagnosed with CCSK. The patient subsequently refused chemotherapy and radiotherapy. During the 2-year follow-up, no recurrence or metastasis was observed. We reviewed the English language literature on adult CCSK published in the PubMed database. A pooled analysis was performed, and the results suggested that an accurate pathological diagnosis of CCSK could be achieved based on microscopy and immunohistochemistry. Nephrectomy and regional lymphadenectomy are the main treatments for adult patients with CCSK. While the value of adjuvant radiotherapy and chemotherapy remains controversial, multimodal oncologic treatment, including surgery and chemotherapy with or without radiation, may be efficacious in preventing local recurrence and distant metastases.

EFEMP1 as a Potential Biomarker for Diagnosis and Prognosis of Osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy. Our previous study revealed an association between the level of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) and the invasion, metastasis, and poor prognosis of OS. However, the exact correlation between the serum EFEMP1 level and OS diagnosis and progression was unclear. This study is aimed at determining the value of the serum EFEMP1 level in the diagnosis and prognosis of OS. Fifty-one consecutive OS patients were prospectively registered in this study. The serum EFEMP1 levels were measured using ELISA at diagnosis, after neoadjuvant chemotherapy, and before and after surgical treatment. Sixty-nine healthy subjects in the control group, nine patients with chondrosarcoma, and 12 patients with giant cell tumor of the bone were also enrolled in this study. Surgical orthotopic implantation was used to generate a mouse OS model, and the correlation between the circulating EFEMP1 levels and tumor progression was examined. Then, OS patients had significantly higher mean serum EFEMP1 levels (7.61 ng/ml) than the control subjects (1.47 ng/ml). The serum EFEMP1 levels were correlated with the Enneking staging system (r = 0.32, P = 0.021) and lung metastasis (r = 0.50, P < 0.001). There was also a correlation between the serum EFEMP1 level and EFEMP1 expression in the respective OS samples (r = 0.49, P < 0.001). Additionally, patients with either chondrosarcoma or giant cell tumor of the bone had significantly higher serum EFEMP1 levels than OS patients. Surgical and chemotherapeutic treatment led to an increase in the serum EFEMP1 levels. Then, the destruction of bone tissues might be one of the factors about the EFEMP1 levels. In the mouse OS model, the serum EFEMP1 level was correlated with tumor progression. Our results suggested that serum EFEMP1 levels might be used to distinguish OS patients from healthy controls and as an indicator for OS lung metastasis. Serum EFEMP1 levels could serve as a new and assisted biomarker for the auxiliary diagnosis and prognosis of OS.