热休克蛋白105在鳞状细胞癌及乳房外Paget病而非基底细胞癌中过表达

Background: Heat shock protein (HSP) 105 is a 105-kDa protein, recently discovered by serological analysis of recom-binant cDNA expression libraries prepared from tumour cells (SEREX), and is still undergoing intensive research. SEREX can define strongly immunogenic tumour antigens that elicit both cellular and humoral immunity. Previous studies have shown that HSP105 is a cancer testis antigen and is overexpressed in various internal malignancies. The expression of HSP105 has not been studied in skin cancers. Objectives: To assess the expression of HSP105 in skin cancers including extramammary Paget disease (EMPD), cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Methods: Samples of EMPD (n = 25), SCC (n = 23, of which three were metastatic lesions) and BCC (n = 23) were collected from patients treated in our department between January 2002 and December 2004. Western blot and immunohistochemical staining methods were used to investigate the expression of HSP105. Results: Results of Western blot analysis showed overexpression of HSP105 in EMPD and SCC, and minimal expression in BCC. Immunohistochemistry results showed that 56%of EMPD, 60%of primary and 100%of metastatic SCC highly expressed HSP105 while only 13%of BCC lesions showed increased staining. Conclusions: EMPD and SCC overexpress HSP105 while BCC does not. Tumours overexpressing HSP105 present ideal candidates for vaccination by HSP105-derived peptides or DNA.

病灶黏附激酶组成型磷酸化与硬皮病成纤维细胞的肌纤维母细胞分化相关

Most of the cultured scleroderma fibroblasts have been reported to be myofibroblasts that have the ability to express α.smooth muscle actin (αSMA). It is reported that, in human lung fibroblasts, αSMA is induced by transforming growth factor-β.(TGF-β), which requires focal adhesion kinase (FAK) phosphorylation on its Tyr-397 site. In this study, we investigated how αSMA expression is upregulated in cultured scleroderma fibroblasts. 4-amino-5-(4-chlorophenyl)7-(butyl)pyrazolo 3,4-d pyrimidine, which is a pharmacologic inhibitor of FAK/Src, markedly diminished upregulated αSMA expression in scleroderma fibroblasts as well as in normal fibroblasts stimulated with TGF-β. Likewise, αSMA expression was significantly reduced in sclerderma fibroblasts transfected with kinase-deficient FAK mutant. FAK phosphorylation levels on Tyr-397 in scleroderma fibroblasts were significantly higher than those in normal fibroblasts. Both αSMA expression and FAK phosphorylation levels in scleroderma fibroblasts were markedly diminished by the treatment with TGF-βantisense oligonucleotide. These results indicate that the constitutive phosphorylation of FAK, which is possibly because of the autocrine TGF-βsignaling, may play an important role in αSMA expression in scleroderma fibroblasts.

系统性硬皮病中同型性风湿因子和抗-AGIgG抗体的表达

Background: Rheumatoid factor isotypes and anti-agalactosyl IgG antibodies (anti-AG IgG) have been reported to be detected and correlated with the diseas e activity in some collagen diseases. Objectives: To study the frequency and the clinical significance of IgM, IgG and IgA rheumatoid factor (IgM-RF, IgG-RF and IgA-RF) and anti-AGIgGin patientswith systemic sclerosis (SSc). Methods : Seventy-nine serum samples from patients with SSc were examined by specific enzyme-linked immunosorbent assays. Results: The levels of IgM-, IgG-, IgA -RF and anti-AG IgG were significantly higher in SSc patients than in normal healthy controls. The levels of IgM-and IgA-RF were significantly higher in patients with diffuse cutaneous SSc than in those with limited cutaneous SSc. I gM-, IgG-and IgA-RF and anti-AG IgG were significantly elevated in 39% , 32% , 23% and 35% of 79 SSc patients, respectively. The prevalence of pul monary fibrosis,oesophageal involvement and cutaneous telangectasias in patients with elevated IgA-RF levels was significantly higher than in those with norma l levels. The incidence of pitting scars of digits in those with elevated IgG- RF levels and the incidence of contracture of phalanges in those with elevated I gM-RF levels were significantly higher than in those with normal levels. The f requency of increased erythrocyte sedimentation rate in patientswith elevated Ig G-RF and the frequency of increased C-reactive protein in those with elevate d IgM-RF were significantly greater than in those with normal levels. Conclusi ons: IgM-, IgG-, IgA-RF and anti-AG IgG can be serum indicators of speci fic clinical manifestations in SSc patients.

嗜酸性筋膜炎患者血清金属蛋白酶-1和2组织抑制剂水平的测定

Background: Serum levels of tissue inhibitor ofmetalloproteinases (TIMPs) have been reported to be elevated in patients with various connective tissue diseases. However, there has been no report that evaluates TIMPs in patients with eosinophilic fasciitis (EF). Objectives: To determine serum TIMP-1 and TIMP-2 levels in patients with EF and to investigate their clinical significance. Methods: Immunohistochemical stainings were performed in normal and EF skin samples. Serum TIMP-1 and TIMP-2 levels of 11 patients with EF and 12 healthy individuals were also measured with specific enzyme-linked immunosorbent assays. Results: The fascia of EF patients was stained only by TIMP-1. Serum TIMP-1 levels (mean ±SD) were significantly higher in EF patients than in healthy individuals (206.3 ±65.4 vs. 145.2 ±36.2 ng mL-1, P < 0.01). Serum TIMP-1 levels in EF patients were significantly correlated with serum γ-globulin and IgG levels (r = 0.86, P < 0.05; r = 0.83, P < 0.005, respectively). Conclusions: These results suggest that TIMP-1 is involved in the pathogenesis of EF, and that TIMP-1 may be a useful marker for the disease activity as well as serum γ-globulin or IgG levels.

系统性硬皮病中发生硬化性脂膜炎与肺动脉高压有关

Background: There have been no reports of patients with sclerosing panniculitis and systemic sclerosis (SSc). Objectives: To evaluate the incidence of sclerosing panniculitis in patients with SSc, and to investigate the clinical features of such cases. Methods In total, 128 patients with SSc treated at our clinic were investigated retrospectively. Results SSc patients with sclerosing panniculitis had pulmonary hypertension (PH), especially isolated PH, at a significantly higher incidence than those without. Among the SSc patients with PH, those with sclerosing panniculitis had pulmonary infarctions at a higher incidence than those without. Conclusions: Our results suggest that thrombosis caused by venous hypertension of the leg may be the main cause of PH in patients with SSc and sclerosing panniculitis. Sclerosing panniculitis may be a useful marker of PH in patients with SSc.