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Biomedical subjects

Kai Zhou

Publications and source records attributed to Kai Zhou.

8 recordsLinked to original sources

Processes to activate phase III clinical trials in a Cooperative Oncology Group: the Case of Cancer and Leukemia Group B.

PURPOSE: National Cancer Institute-sponsored cooperative oncology groups are major sponsors of phase III clinical trials, yet the time and steps required to design and activate such studies has not been well studied. We examine the processes and document the calendar time required to activate such studies opened by the Cancer and Leukemia Group B (CALGB). METHODS: Setup steps were documented by (1) interviewing CALGB headquarters and statistical center staff and committee chairs to discover the steps required to transit from concept development to final study activation, (2) reviewing procedure manuals, and (3) inspecting all study records, documents, and e-mails to identify any additional steps. Calendar time was collected for each major process. RESULTS: Thirteen phase III studies were activated by CALGB during the study period of May 2002 to May 2005. More than 370 distinct processes were required for study activation: 317 work steps, 42 decision points, and 29 processing loops. Sixty-three percent of the decision points were outside CALGB. The complete process map measures 243.5" x 41" in 8-point font. Median calendar days to activate a phase III study at CALGB was 580 days (range, 295 to 1,248 days) from concept approval and 784 days (range, 537 to 1,130 days) from initial conception of the study. CONCLUSION: Setup of a phase III study at a major cooperative oncology group is a complex and lengthy process, with the majority of decision points external to the cooperative group. To improve the activation process, research should to be directed toward both internal and external groups and processes.

Biomedical Research↗

Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines.

Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 microM. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC(50)=7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents.

Animals↗

Roots of pioneer trees in the lower sub-tropical area of Dinghushan, Guangdong, China.

Representative pioneer tree root systems in the subtropical area of South China were examined with regard to their structure, underground stratification and biomass distribution. Excavation of skeleton roots and observation of fine roots of seven species including the Euphorbiaceae, Theaceae, Melastomataceae, Lauraceae and Fagaceae families was carried out. The results showed that: (1) Pioneer tree roots in the first stage of natural succession were of two types, one characterized by taproot system with bulky plagiotropic branches; the other characterized by flat root system with several tabular roots. The late mesophilous tree roots were characterized by one obvious taproot and tactic braches roots up and down. Shrub species roots were characterized by heart fibrous root type featured both by horizontally and transversally growing branches. Root shapes varied in different dominant species at different stages of succession. (2) Roots of the different species varied in the external features-color, periderm and structure of freshly cut slash. (3) In a set of successional stages the biomass of tree roots increased linearly with the age of growth. During monsoon, the total root biomass amounted to 115.70 t/ha in the evergreen broad-leaved forest; 50.61 t/ha in needle and broad-leaved mixed forest dominated by coniferous forest; and 64.20 t/ha in broad-and needle-leaved mixed forest dominated by broad-leaved heliophytes, and are comparable to the underground biomass observed in similar tropical forests. This is the first report about roots characteristics of forest in the lower sub-tropical area of Dinghushan, Guangdong, China.

Biomass↗

Hepatitis C virus infection in former commercial plasma/blood donors in rural Shanxi Province, China: the China Integrated Programs for Research on AIDS.

BACKGROUND: Unsafe practices during illegal plasma donation in the late 1980s and early 1990s spread bloodborne infections in central China. METHODS: A cross-sectional survey of a random sample of 538 adult residents of 12 villages in rural Shanxi Province, where there had been an illegal commercial plasma-collection center, was conducted in 2003. Structured questionnaires were administered, and blood samples were tested for hepatitis C virus (HCV) antibodies. RESULTS: HCV seroprevalence rates were 8.2% in all subjects, 27.7% in former commercial plasma/blood donors, and 2.6% in nondonors. Selling blood or plasma was the strongest independent predictor of HCV seropositivity (odds ratio [OR], 14.4 [95% confidence interval {CI}, 7.1-31.6]). A history of blood transfusion was also independently associated with HCV seropositivity (OR, 8.3 [95% CI, 2.1-32.0]). Plasma donors had a higher risk of being HCV seropositive than did whole-blood donors (OR, 7.6 [95% CI, 2.9-20.9]), and female donors had a lower risk than did male donors (OR, 0.32 [95% CI, 0.12-0.80]). The strength of the association between selling blood and HCV seropositivity was weaker when plasma donors were excluded (OR, 8.0 vs. 14.4). CONCLUSIONS: Unsafe practices during illegal plasma donation led to a high risk of HCV seropositivity for donors during the 1980s and 1990s. Failure to screen for HCV increased the risk of seropositivity for transfusion recipients during this same period. China has taken steps to halt illegal plasma collection and to improve blood-banking methods. However, there will be an ongoing challenge to care for patients with HCV infection, even as its incidence decreases.

Adult↗

A functional interaction between RHA and Ubc9, an E2-like enzyme specific for Sumo-1.

RNA helicase A (RHA) is a member of the DEAH helicase family of proteins. Recent studies imply the role of RHA in the regulation of the topology of chromatin DNA, which could influence diverse nuclear processes such as transcription activity of the chromatin DNA and chromosome condensation. We previously reported that Ubc9, an E2-like enzyme specific for small ubiquitin-like modifier 1 (Sumo-1), is required for the interaction between RHA and topoisomerase IIalpha. Here, we describe that Ubc9 is a novel factor that functionally interacts with RHA and activates the transcription activity of RHA, measured in the CREB-mediated pathway. We demonstrate that the N-terminal domain of RHA, encompassing amino acid residues 1-137, is sufficient for its interaction with Ubc9. Our data also show that interaction with Ubc9 leads to the Sumo-1 conjugation of RHA both in vitro and in vivo. However, the catalytic activity of Ubc9 seems to be dispensable for the transcription activation activity of RHA. Our observation suggests multiple roles for Ubc9 in the regulation of the RHA function.

Amino Acid Sequence↗

The humoral and cellular immune responses in mice induced by DNA vaccine expressing the sporozoite surface protein of Cryptosporidium parvum.

Cryptosporidiosis, a protozoan disease, is caused by Cryptosporidium parvum in animals and humans. To study the humoral and cellular immune responses induced by DNA vaccine expressing the sporozoite surface protein, CP15/60, of Cryptosporidium parvum, the recombinant plasmid containing the CP15/60 gene was injected into tibialis a interior muscle of BALB/c mice. The mice were subsequently given booster doses twice at 3-week intervals. The humoral and cellular immune responses were detected at different times after immunization. The mice were then challenged by inoculation of 1 x 10(6) oocysts of C. parvum. The experimental results have shown that the recombinant plasmid can induce corresponding specific immune responses and thus protect the mice from challenge of the oocysts, suggesting that the recombinant plasmid could be a potential candidate of DNA vaccine.

Animals↗

RNA helicase A interacts with dsDNA and topoisomerase IIalpha.

RNA helicase A (RHA) is a multifunctional protein involved in various nuclear processes such as transcription and RNA export. It is believed that the interacting factors play important roles in determining the functional specificity of RHA. Here we show that RHA directly interacts with double-stranded (ds) nucleic acids (NAs) and assembles complexes with topoisomerase IIalpha. First, electrophoresis mobility shift assays demonstrate that RHA interacts with dsDNAs of different lengths ranging from 15 to 104 bp. Secondly, the binding of RHA to closed circular dsDNA stimulates the relaxation reaction catalyzed by either calf thymus topoisomerase I or HeLa topoisomerase IIalpha. Thirdly, immunoprecipitation, coupled with western blot analysis using anti-RHA and anti-topoisomerase IIalpha antibodies, shows that RHA and topoisomerase IIalpha assemble a complex in the presence of as yet unknown RNA molecules and additional protein factors such as Ubc9. Our observation suggests physical and functional interaction between RHA and topoisomerase IIalpha, which, perhaps, play important roles in regulating chromatin structure. The putative role of RHA-topoisomerase IIalpha complex in RNA polymerase II-mediated transcription is discussed.

Adenosine Triphosphatases↗

[Effects of fumaric acid esters on differentiation of dendritic cells in vitro]

OBJECTIVE: To investigate the effect of anti-psoriatic drug fumaric acid esters (FAE) on the differentiation of dendritic cells (DC). METHODS: Dendritic cells were obtained by differentiating human monocytes in vitro. Flow cytometry was used to analyse the effect of FAE on cell surface expression of CD1a, CD14, CD40, CD80, CD86 and HLA-DR by monocyte-derived dendritic cells (MoDC). Mixed lymphocyte reaction (MLR) was made to demonstrate the influence of FAE on T cell stimulatory activity of MoDC. RESULTS: Dimethylfumarate and methylhydrogenfumarate-calcium-salt (0.01 approximate, equals 100 mg/L) inhibited MoDC differentiation as well as reducing the capacity of MoDC to stimulate lymphocytic proliferation in MLR. CONCLUSION: The mode of action of FAE in pso riasis may be mediated by inhibition of DC differentiation.

Journal Article↗