BackgroundSystemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. Although the involvement of connective tissue growth factor (CTGF/CCN2) has been well-documented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully investigated. Our aim was to examine the therapeutic potential of CTGF blockade in a preclinical model of SSc using two approaches: smooth muscle cell fibroblast-specific deletion of CTGF (CTGF knockout (KO)) or a human anti-CTGF monoclonal antibody, FG-3019.MethodsAngiotensin II (Ang II) was administered for 14 days by subcutaneous osmotic pump to CTGF KO or C57BL/6 J mice. FG-3019 was administered intraperitoneally three times per week for 2 weeks. Skin fibrosis was evaluated by histology and hydroxyproline assay. Immunohistochemistry staining was used for alpha smooth muscle actin (αSMA), platelet-derived growth factor receptor β (PDGFRβ), pSmad2, CD45, von Willebrand factor (vWF), and immunofluorescence staining was utilized for procollagen and Fsp1.ResultsAng II-induced skin fibrosis was mitigated in both CTGF KO and FG-3019-treated mice. The blockade of CTGF reduced the number of cells expressing PDGFRβ, procollagen, αSMA, pSmad2, CD45, and Fsp1 in the dermis. In addition, inhibition of CTGF attenuated vascular injury as measured by the presence of vWF-positive cells.ConclusionsOur data indicate that inhibition of CTGF signaling presents an attractive therapeutic approach in SSc.

BONENAVI version 2 is an effective computer-assisted diagnosis system for bone scanning, but the drawbacks of bone scanning remain unresolved.

Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatment options. Activated fibroblasts are the key effector cells in SSc responsible for the excessive production of collagen and the development of fibrosis. PDGF, a potent mitogen for cells of mesenchymal origin, has been implicated in the activation of SSc fibroblasts. Our aim was to examine the therapeutic potential of crenolanib, an inhibitor of PDGF receptor signaling, in cultured fibroblasts and in angiotensin II (Ang II)-induced skin and heart fibrosis. Crenolanib effectively inhibited proliferation and migration of SSc and healthy control (HC) fibroblasts, and attenuated basal and TGF-β-induced expression of CCN2/CTGF and periostin. In contrast to HC fibroblasts, SSc fibroblasts proliferated in response to PDGFAA, while a combination of PDGFAA and CCN2 was required to elicit a similar response in HC fibroblasts. Importantly, PDGFRα mRNA correlated with CCN2 and other fibrotic markers in the skin of SSc patients. In mice challenged with Ang II, PDGFRα-positive cells were increased in the skin and heart. These PDGFRα-positive cells co-localized with PDGFRβ, procollagen and periostin. Treatment with crenolanib attenuated the skin and heart fibrosis. Our data indicate that inhibition of PDGF signaling presents an attractive therapeutic approach for SSc.

PET/CT may be a useful screening tool for patients with clinically suspected PNS who do not exhibit well-characterized paraneoplastic antibodies. Therefore, we recommended that PET/CT should be performed for patients with clinically suspicious PNS regardless of the presence of well-characterized paraneoplastic antibodies.

Dual-time-point FDG PET/CT is not useful for discriminating between benign and malignant salivary gland tumors, because benign tumors also show high FDG uptake, which increases in the delayed phase.