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Objective To evaluate the effectiveness and safety of gefitinib retreatment beyond progression(GRBP)in non-small cell lung cancer(NSCLC)patients with rare EGFR mutations.Methods We retrospectively analyzed six rare-EGFR-mutation NSCLC patients from Jan 2011 to Dec 2015.Those patients had previous disease control and then disease progression according to Response Evaluation Criteria in Solid Tumors version 1.1(RECIST v1.1)after taking oral gefitinib 250 mg once a day.After that,continuing gefitinib was decided by clinicians′ experience at the same treatment option.The primary endpoints were response rate(RR),overall survival(OS),the first and second progression-free survival(PFS-1 and PFS-2).Safety was assessed according to the NCI-CTCAE version 4.0.Results After initial treatment of gefitinib,4 patients achieved partial response(PR)and 2 patients showed stable disease(SD),with RR being 66.7％.The median PFS-1 and PFS-2 were 10 months(95％CI 6.6-13.4)and 9 months(95％CI 6.9-11.1),respectively.The median OS time was 28 months(95％CI 10.4-45.6).The most common treatment-related adverse events were fatigue,diarrhea,rash,itching and elevated transaminases.Conclusion In our study,gefitinib retreatment beyond disease progression is effective with a manageable tolerability profile.
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Recombinant adeno-associated viral (rAAV) vectors are promising vectors for human gene therapy. However, AAV-mediated gene transduction can be hampered because of the pre-existing neutralized natural antibodies (NAbs) in primates. We evaluated transduction efficiency of rAAV6 expressing human alpha-1-anti-trypsin (hAAT) vectors in murine models, and found that these vectors showed stable and high levels of transgene expression. Fluorescence imaging showed that AAV6 expressing enhanced green fluorescent protein (eGFP) by intravenous administration predominantly targeted the liver, but led to self-limited hepatitis. Besides, our study evaluated epidemiology of anti-AAV6 NAb in non-human primates (NHPs) by NAb assay in vitro. The result indicated that 52.17% of NHPs had detectable NAb at 1:5 dilution rate. In vivo passive transfer experiment showed that AAV6 specific neutralizing antibody, even though with low NAb titer, could significantly inhibit rAAV6 transduction.
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Animales , Masculino , Ratones , Traslado Adoptivo , Anticuerpos Neutralizantes , Alergia e Inmunología , Dependovirus , Genética , Metabolismo , Técnicas de Transferencia de Gen , Terapia Genética , Vectores Genéticos , Genética , Proteínas Fluorescentes Verdes , Genética , Metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , alfa 1-Antitripsina , Genética , MetabolismoRESUMEN
BACKGROUND: Root resorption is the treatment of malocclusion deformity correction in a common adverse reaction, and associated factors can be divided into biological and mechanical factors.OBJECTIVE: To explore the biological and mechanical factors of the root resorption caused by orthodontic treatment, so as to reduce the treatment risks.METHODS: With key words "root resorption, biomechanics", a computer-based online search of PubMed database (1990-01/2009-05) and CNKI database (1990-01/2009-05) was performed for articles published in English and Chinese. Root resorption in Levander & Malmgren rating system was used as the evaluation index. The orthodontic treatment-related content was included, and other aspects of research were excluded.RESULTS AND CONCLUSION: A total of 72 articles were collected, and according to inclusion and exclusion criteria, 31 were included for analysis. Root resorption is a common phenomenon associated with orthodontic treatment, The factors relevant to root resorption can be divided into biological and mechanical factors, which are associated with an increased or decreased risk of root resorption during orthodontic treatment. Orthodontic therapy of patients with increased risk of root resorption should be carefully planned. Medical history, medication intake, family history, tooth and root morphology, oral health and habits must be considerate. The standard procedure to monitor apical root resorption is a radiographic examination after 6 months of treatment. In teeth with enhanced risk, a 3-month radiographic follow-up is recommended. The use of anti-inflammatory drugs might suppress root resorption induced by orthodontic therapy, although no study is conclusive enough to indicate a protocol for patients with enhanced dsk. In the event of multiple external root resorption, the diagnostic procedure should focus on the exclusion of the local factors and its associations (such as magnitude, duration and type of orthodontic force, periodontal disease, root form) that might lead to external root resorption. Systemic disorders associated with phosphorus-calcium metabolic alterations are also suspected.Orthodontic treatment may cause a certain degree of root resorption, especially in patients with high-risk factors, but this risk can be minimized by the control of force and the close monitor of treatment process.