Therapeutic Effect of Dimethyl Dimethoxy Biphenyl Dicarboxylate on Collagen-Induced Arthritis in Rats

Objective:To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate(DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis(CIA).Methods:Wistar rat model of CIA was set up using bovine collagen type Ⅱ.Fifty rats were divided into five groups randomly:normal,CIA model,DDB treatment,methotrexate(MTX) treatment,and combined DDB+MTX treatment.Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints.Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining.Plasma levels of vascular endothelial growth factor(VEGF),platelet derived growth factor,interleukin-8(IL-8),IL-4,tumor necrosis factor α(TNF-α),and cyclooxygenase-2(COX-2) were quantified by enzyme-linked immunosorbent assay.Nitric oxide levels were detected by Griess reagent.Results:Compared with the CIA model group,a remarkable reduction in various angiogenic(VEGF and IL-8) and inflammatory mediators(TNF-α,IL-4 and COX-2) after treatment with DDB either alone or combined with MTX(P0.05 or P0.01).Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect.The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal.Conclusion:Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis(RA) compared with a choice drug(MTX) and it may be offered as a second-line drug in the treatment of RA.     

Pseudo-angiomatous hyperplasia of mammary stroma: a case with gigantomastia

Pseudo-angiomatous hyperplasia of mammary stroma (PASH) is a histopathological entity which is a microscopic fortuitous finding in mammary biopsies performed for different reasons. It may be symptomatic and appears then as a palpable lump. The term pseudo-angiomatous emphasizes the characteristic aspect of the stroma simulating a vascular tumor. We report a case of PASH in a 71 year-old woman who presented a recurring breast mass with rapid swelling of the mammary gland (70 x 60 x 20 cm) treated by mastectomy. PASH must be distinguished from a well-differentiated angiosarcoma. It is ruled out by immunohistochemistry.     

Analysis of the p21 gene in gliomas

The p21 gene encodes a cyclin dependent kinase inhibitor protein (p21) which has a tumor suppressive activity in a variety of tumor cell lines. Since, the p21 gene is up-regulated by the p53 tumor suppressor gene, which is frequently mutated in gliomas, acting therefore in the same control pathway, it constitutes a good candidate gene to be also inactivated in these tumors. To test this hypothesis, DNAs from 81 gliomas (48 glioblastomas, 11 anaplastic astrocytomas, 10 low-grade astrocytomas, 12 oligodendrogliomas and mixed gliomas), were investigated for mutations in the p21 coding sequence by denaturant gradient gel electrophoresis followed by sequencing. All these tumors have been previously screened for p53 mutations. Three different DNA variants were identified on codon 31 (17 cases), 27 (1 case) and 117 (1 case) and shown to be also present in matching constitutional DNA, suggesting they were polymorphisms. None of the tumors demonstrated a somatic mutation. No significant correlation between the presence of a p21 variant and the p53 mutation tumor status was observed. In conclusion, mutation in the p21 gene unlikely contributes to the development of gliomas.     

Prognostic stratification of gliomatosis cerebri by IDH1R132H and INA expression

Gliomatosis cerebri (GC) constitutes a heterogeneous group of conditions involving diffuse neoplastic glial cell infiltration of the brain. Management is difficult and an obvious challenge is to identify prognostic factors. Alpha-internexin (INA) expression, which is closely related to the 1p19q codeletion, is a strong prognostic marker in oligodendroglial tumors. Similarly, the R132H isocitrate dehydrogenase 1 IDH1 mutation, which can now be detected by use of a specific antibody, predicts better outcome in gliomas. In a retrospective series of 40 GC treated with up-front chemotherapy, we analyzed IDH1(R132H) mutant protein and INA immunohistochemical expression and correlated it with outcome; 17/40 GC expressed IDH1(R132H) and 10/40 GC expressed INA. IDH1(R132H) staining was strongly related to progression-free survival (42.3 vs. 15.5 months for positive IDH1(R132H) vs. negative tumors; P < 0.0001) and overall survival (73.9 vs. 23.6 months; P < 0.0001). This effect was independent of grade, histologic subtype, and INA expression (P < 0.001). Combined expression of IDH1(R132H) and INA was strongly associated with response to chemotherapy (100% vs. 36%; P = 0.003). These data strongly suggest that INA and IDH1(R132H) mutant protein immunohistochemical analysis is of a great prognostic value in biopsied GC.