ABSTRACT
BACKGROUND: Although carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are useful markers for extramammary Paget disease (EMPD), serum CEA and CYFRA levels are not elevated in most patients with EMPD without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. OBJECTIVES: To identify further useful biomarkers for the detection of EMPD, including early lesions, and to study the clinical implications of cfDNA in EMPD. METHODS: cfDNA were isolated from serum of patients with EMPD with and without metastasis, and from healthy volunteers. Serum extracts were amplified using polymerase chain reaction. RESULTS: Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Serum cfDNA was a better diagnostic marker for the presence of EMPD than serum CYFRA. Moreover, the postoperative serum cfDNA levels were significantly lower than those from the preoperative samples, and the change in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. CONCLUSIONS: Taking the evidence together, serum cfDNA levels may be a useful marker for diagnosis and disease progression in EMPD. What's already known about this topic? Serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are not elevated in most patients with extramammary Paget disease (EMPD) without metastasis. Cell-free (cf)DNA has attracted attention as an indicator of clinical conditions in several cancers. There are few reports of the clinical implications of cfDNA in dermatology. What does this study add? Serum cfDNA levels were significantly elevated in patients with EMPD with or without metastasis compared with those in healthy controls. Postoperative serum cfDNA levels were significantly lower than those from the preoperative samples. Changes in serum cfDNA levels reflected the clinical courses of patients with EMPD treated with chemotherapy. What is the translational message? Serum cfDNA levels in patients with EMPD are a useful marker for the detection of EMPD, including localized EMPD. Changes in serum cfDNA levels in an individual patient may reflect the clinical course of EMPD.
Subject(s)
Biomarkers, Tumor/blood , Cell-Free Nucleic Acids/blood , Paget Disease, Extramammary/diagnosis , Skin Neoplasms/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/blood , Biomarkers, Tumor/genetics , Case-Control Studies , Disease Progression , Female , Humans , Keratin-19/blood , Male , Middle Aged , Paget Disease, Extramammary/blood , Paget Disease, Extramammary/genetics , Paget Disease, Extramammary/surgery , Postoperative Period , Preoperative Period , Skin/pathology , Skin Neoplasms/blood , Skin Neoplasms/genetics , Skin Neoplasms/surgery , Young AdultABSTRACT
OBJECTIVE: Chondrocyte differentiation is crucial for long bone growth. Many cartilage extracellular matrix (ECM) proteins reportedly contribute to chondrocyte differentiation, indicating that mechanisms underlying chondrocyte differentiation are likely more complex than previously appreciated. Angiopoietin-like protein 2 (ANGPTL2) is a secreted factor normally abundantly produced in mesenchymal lineage cells such as adipocytes and fibroblasts, but its loss contributes to the pathogenesis of lifestyle- or aging-related diseases. However, the function of ANGPTL2 in chondrocytes, which are also differentiated from mesenchymal stem cells, remains unclear. Here, we investigate whether ANGPTL2 is expressed in or functions in chondrocytes. METHODS: First, we evaluated Angptl2 expression during chondrocyte differentiation using chondrogenic ATDC5 cells and wild-type epiphyseal cartilage of newborn mice. We next assessed ANGPTL2 function in chondrogenic differentiation and associated signaling using Angptl2 knockdown ATDC5 cells and Angptl2 knockout mice. RESULTS: ANGPTL2 is expressed in chondrocytes, particularly those located in resting and proliferative zones, and accumulates in ECM surrounding chondrocytes. Interestingly, long bone growth was retarded in Angptl2 knockout mice from neonatal to adult stages via attenuation of chondrocyte differentiation. Both in vivo and in vitro experiments show that changes in ANGPTL2 expression can also alter p38 mitogen-activated protein kinase (MAPK) activity mediated by integrin α5ß1. CONCLUSION: ANGPTL2 contributes to chondrocyte differentiation and subsequent endochondral ossification through α5ß1 integrin and p38 MAPK signaling during bone growth. Our findings provide insight into molecular mechanisms governing communication between chondrocytes and surrounding ECM components in bone growth activities.
Subject(s)
Angiopoietin-like Proteins/physiology , Bone Development/physiology , Angiopoietin-Like Protein 2 , Angiopoietin-like Proteins/metabolism , Animals , Animals, Newborn , Cell Differentiation/physiology , Cells, Cultured , Chondrocytes/cytology , Chondrocytes/metabolism , Chondrogenesis/physiology , Enzyme Inhibitors/pharmacokinetics , Femur/growth & development , Imidazoles/pharmacokinetics , MAP Kinase Signaling System/physiology , Matrilin Proteins/metabolism , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Electron , Pyridines/pharmacokinetics , Tibia/growth & developmentABSTRACT
A case of carcinoma of the tongue treated with neoadjuvant chemotherapy has been reported. The patient was a 61-year-old man complaining of tumor and contact pain at the left margin of the tongue. The tumor was oval and elastic soft with pedicle, measuring 26 X 16 X 8 mm in size. The tumor was histopathologically diagnosed as a highly differentiated squamous cell carcinoma. The patient was treated with CDDP (75 mg/body) and PEP (5 mg/body) for 5 days. After two trials with about a 3-week interval, treatment result showed partial response. This result demonstrated that combination chemotherapy of CDDP and PEP is an effective regimen for remission neoadjuvant chemotherapy in patients with squamous cell carcinoma.
