ABSTRACT
Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.
Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Clinical Trials as Topic , Marketing , Neoplasms/drug therapy , Research Design , United States , United States Food and Drug AdministrationABSTRACT
<p><b>OBJECTIVE</b>To observe changes of bulbar conjunctival microcirculation in rabbits of five kinds subtypes of blood stasis syndrome (BSS), and to analyze their different properties.</p><p><b>METHODS</b>Totally 60 Japanese big-ear rabbits were randomly divided into six groups, i.e., qi deficiency blood stasis group, qi stagnation blood stasis group, cold coagulation blood stasis group, heat toxin blood stasis group, external injury blood stasis group, and the normal control group, 10 in each group. Changes of rabbit bulbar conjunctiva microcirculation were observed before and after modeling.</p><p><b>RESULTS</b>Compared with the normal control group, the total integral of bulbar conjunctiva microcirculation obviously increased in the 5 BSS groups (P < 0.05). There was no statistical difference among the 5 BSS groups (P > 0.05). But there was statistical difference in any concrete integral among the 5 BSS groups (P < 0.05). Thickening blood vessels and errhysis of vascular walls were dominant in the heat toxin blood stasis group. Ischemia, partial cystic dilatation, vascular engorgement and twist were dominant in the qi deficiency blood stasis group. Partial vascular buckling, aneurysmal changes, flow velocity slowed down were dominant in the qi stagnation blood stasis group. Vascular buckling, hyperemia, vascular engorgement, blood flow slowed down were dominant in the external injury blood stasis group. Vascular buckling, ischemia, dark color were dominant in the cold coagulation blood stasis group.</p><p><b>CONCLUSION</b>Changes of bulbar conjunctival microcirculation were different in 5 kinds of BSS types, which could reflect their various features.</p>
Subject(s)
Animals , Female , Male , Rabbits , Conjunctiva , Diagnosis, Differential , Medicine, Chinese Traditional , MicrocirculationABSTRACT
Objective To investigate the role of apolipoprotein D (ApoD) in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). Methods The expression of ApoD protein in renal cystic tissues of ADPKD patients was examined by immunofluorescence and Western blotting analysis. Western blotting analysis and real-time PCR were used to detect the expression of ApoD protein and mRNA in the renal tissues of Han: SPRD rats. The cystic lining immortalized epithelial cells (WT9-12 cells) of ADPKD were stimulated with human recombinant ApoD protein and their proliferation was examined by MTT assay; flow cytometry was used to determine the cell apoptosis and cell cycle distribution. Results Immunohistochemisty and Western blotting analysis showed that ApoD expression was significantly lower in the renal tissues of ADPKD patients than that in healthy controls, and that in the Han: SPRD cy/+ rats was significantly lower than that in the Han: SPRD +/+ rats (P<0. 05, P<0. 01). ApoD mRNA expression in the kidneys of Han: SPRD cy/+ rats of 8, 12, 16, and 24 weeks old was significantly lower than that of Han: SPRD +/+ rats of same ages (P<0. 05). Recombinant ApoD protein at 100, 200, and 400 ng/ml inhibited the proliferation of WT9-12 cells by 8. 21%, 7. 59% and 8. 07% after 48 h stimulation (P<0. 05), and by 8. 62%, 6. 43% and 9. 42% after 72 h stimulation, respectively (P<0. 05). Treatment with 400 ng/ml human recombinant ApoD protein for 72 h increased Gi phase WT9-12 cells by 8. 26% and decreased S phase cells by 8. 09% (P<0. 05), but it had no significant effect on cell apoptosis. Conclusion ApoD may inhibit WT9-12 cell proliferation by regulating cell cycle, and decreased ApoD expression may participate in the pathogenesis of ADPKD.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the association of IL-1beta+3953, TNFbeta+252 and IL-10-592 polymorphisms with serum lipoprotein levels in Chinese Han population in Guangdong Province.</p><p><b>METHODS</b>A total of 428 individuals of Han nationality from Guangdong Province were enrolled in this study. The genotypes of IL-1beta+3953, TNFbeta+252 and IL-10-592 sites were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The serum concentrations of total cholesterol (TC), TG, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very low density lipoprotein (VLDL) were determined using an automatic biochemistry analyzer.</p><p><b>RESULTS</b>The concentrations of TC and LDL in individuals of TNFbeta+252GA genotype was significantly higher than that in TNFbeta+252AA genotype (t=-2.406, P=0.017; t=-2.516, P=0.012). The concentration of LDL in IL-10+3953CT genotype was significantly higher than that in IL-10+3953CC genotype (2.743-/+0.723 vs 2.502-/+0.699 mmol/L, t=-2.639, P=0.009). No significant differences were found in TG, TC, HDL, LDL and VLDL between the 3 genotypes (P>0.05).</p><p><b>CONCLUSION</b>The polymorphisms of proinflammatory cytokines are related to the serum lipoprotein level in these subjects. The T allele in IL-1beta+3953 and the G allele in TNFbeta+252 are positively correlated to dyslipidemia.</p>