Fatal familial insomnia presenting with posture instability and retropulsion: a case report and literature review / 中华神经科杂志

Objective:To explore the clinical and genetic features in a case of fatal familial insomnia (FFI).Methods:A case of 39 years old woman diagnosed as progressive supranuclear palsy based on the preliminary manifestation of imbalance and frequent falls was reported. The clinical features, imaging characteristics, electroencephalogram and polysomnography of the patient were analyzed, and the blood samples from the patient were collected for the sequencing of prion protein (PRNP) gene.Results:This patient is a middle-aged woman, whose clinical manifestations were posture instability and retropulsion, rapid progressive dementia and dysarthria, sleep-related dyspnea and laryngeal stridor, with autonomic symptoms of hypertension, sweating, tachycardia and irregular breathing. The results of PRNP gene sequencing revealed that the mutation of gene D178N/129M was detected.Conclusions:Laryngeal stridor plays an important role in the diagnosis of FFI. Posture instability and retropulsion are relatively rare in the FFI clinical symptom spectrum. Here, a case of FFI presenting with posture instability and retropulsion during the early stage with Met/Met at the polymorphic codon 129 is reported in China.

Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12 / 医学前沿

Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%-85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.

Preparation and identification of a 9B9 monoclonal antibody specifically targeting EGFRvⅢ/EGFR / 中国肿瘤生物治疗杂志

Objective:To prepare and identify monoclonal antibody specifically targeting epidermal growth factor receptor(EGFR) and(or) epidermal growth factor receptor vⅢ(EGFRvⅢ),and to investigate its inhibitory effects on human hepatocellular carcinoma Huh7-EGFRvⅢ cell-and epidermal carcinoma A431 cell-implanted tumors in nude mice.Methods: BALB/c mice were immunized with 3T3 cells stably transfected with EGFRvⅢ(3T3-EGFRvⅢ).Immunized spleen cells were fused with myeloma SP2/0 cells,and anti-EGFRvⅢ monoclonal antibody positive hybridoma cells(named 9B9 antibody and 9B9 cells,respectively) were selected and identified by ELISA.The specific interaction between 9B9 antibody and EGFRvⅢ/EGFR antigen was detected by Western blotting and immunofluorescence assay.Huh7-EGFRvⅢ cell-(human hepatocellular carcinoma Huh7 cells stably transfected with EGFRvⅢ) and epidermal cell carcinoma A431 cell-bearing mouse models were established and were divided into PBS group,Cetuximab group and 9B9 antibody group.Then,anti-tumor effect of 9B9 antibody was examined and compared with those of PBS and Cetuximab.Results: A monoclonal antibody,named 9B9 antibody,was obtained by hybridoma technique and it reacted with both EGFRvⅢ antigen and EGFR antigen as detected by Western blotting and immunofluorescence.The inhibitory rates of Cetuximab and 9B9 antibody against Huh7-EGFRvⅢ cells-implanted tumors were 42% and 46%,respectively,and those against A431 cells-implanted tumors were 85% and 86%,respectively.Conclusion: 9B9 monoclonal antibody can effectively inhibit the growth of human hepatocellular carcinoma cell-and epidermal cell carcinoma cell-implanted tumors,and the effects resemble that of Cetuximab.