1,721,082 research outputs found
Selection of sAPRIL-BP.
<p>(A) The binding affinity of phage clones No.1–20 for sAPRIL were determined by ELISA. Clone 21 was used as a positive control. The fold change of the optical density was normalized to the positive control. Clones that had at least a 6-fold greater affinity than the positive control were considered ‘positive’ for sAPRIL binding. (B) Three binding peptides were synthesized and their binding affinity with sAPRIL (black bars) was determined and compared with the negative control (NC) using ELISA. Cross-reactivity was assessed by measuring the binding affinity to BAFF (grey bars). (C) Clone BP1 (sAPRIL-BP) was mixed with sAPRIL at different doses to compete for binding with fixed LOVO cells.</p
Identification of the sAPRIL binding peptide and its growth inhibition effects in the colorectal cancer cells.
A proliferation-inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) super family. It binds to its specific receptors and is involved in multiple processes during tumorigenesis and tumor cells proliferation. High levels of APRIL expression are closely correlated to the growth, metastasis, and 5-FU drug resistance of colorectal cancer. The aim of this study was to identify a specific APRIL binding peptide (BP) able to block APRIL activity that could be used as a potential treatment for colorectal cancer.A phage display library was used to identify peptides that bound selectively to soluble recombinant human APRIL (sAPRIL). The peptides with the highest binding affinity for sAPRIL were identified using ELISA. The effects of sAPRIL-BP on cell proliferation and cell cycle/apoptosis in vitro were evaluated using the CCK-8 assay and flow cytometry, respectively. An in vivo mouse model of colorectal cancer was used to determine the anti-tumor efficacy of the sAPRIL-BP.Three candidate peptides were characterized from eight phage clones with high binding affinity for sAPRIL. The peptide with the highest affinity was selected for further characterization. The identified sAPRIL-BP suppressed tumor cell proliferation and cell cycle progression in LOVO cells in a dose-dependent manner. In vivo in a mouse colorectal challenge model, the sAPRIL-BP reduced the growth of tumor xenografts in nude mice by inhibiting proliferation and inducing apoptosis intratumorally. Moreover, in an in vivo metastasis model, sAPRIL-BP reduced liver metastasis of colorectal cancer cells.sAPRIL-BP significantly suppressed tumor growth in vitro and in vivo and might be a candidate for treating colorectal cancers that express high levels of APRIL
Serological markers “CEA test & sAPRIL test” in Iraqi patients with colon cancer
Background: Colonic cancer is a very common disease world-wide being fourth most common cancer characterized by abnormal proliferation of the inner wall of colon then taking full colon wall thickness then spreading to surrounding lymph nodes and tissues and finally distant metastasis. It is one of most complicated diseases with debilitating symptoms which becomes more sever , prominent and specific with advancing stage with high percent of fatality and relatively short survival if diagnosed late or if left untreated.
Objective: To evaluate the efficacy of serum CEA & sAPRIL levels in the diagnosis and screening of colon cancer and their validity for this.
Patients and methods: This study was applied on 35 patients with colonic cancer, 35 patients with benign polyps and 15 negative controls. All individuals were subjected to blood sampling for measuring their serum CEA & sAPRIL using ELISA technique.
Results: In this study, majority of patients with colon cancer were presented at ages between 53-82 years of age (mean 68.5±6.4 years). Serum levels of sAPRIL & CEA were significantly elevated in those patients with advancing stages (C & D) compared with stages (A & B) and lower levels were found in patients who had surgical removal of tumor or received chemotherapy. Also a positive relation was found between sAPRIL & CEA with alcohol intake and smoking
Conclusion: according to this study sample it was found that sAPRIL and CEA together are strong indicators for colon cancer screening & diagnosis, and by this will reduce the need for more invasive screening & diagnostic tools
Effect of sAPRIL-BP on cell cycle and apoptosis of LOVO cells.
<p>LOVO cells were treated with the indicated doses of sAPRIL-BP for 48 h. Cells were stained with PI for cell cycle analysis (A and B) and PI + Annexin V for apoptosis analysis (C and D) by flow cytometry. *<i>p</i> <0.05 compared to Vehicle control; #<i>p</i> <0.05 compared to the low dose group.</p
<i>In vivo</i> effect of sAPRIL-BP on liver metastasis.
<p>LOVO cells were injected into the spleens of nude mice to observe experimental liver metastasis. Three weeks after injection, the mice were divided into 3 groups (N = 5) and treated with PBS (control), low (20 mg/kg), or high (40 mg/kg) doses of sAPRIL-BP every other day. Mice were sacrificed after two weeks of treatment with sAPRIL-BP. (A) Representative pictures of the metastatic liver tumors from each group are shown. (B) Numbers of metastatic nodules per mouse were recorded. *<i>P</i> <0.05 compared to control. #<i>P</i> <0.05 compared to the low dose group. (C) Numbers of metastatic nodules with the indicated size were recorded. Total numbers of metastatic nodules: n = 197 (Con), n = 130 (20 mg/kg), and n = 84 (40 mg/kg).</p
<i>In vivo</i> effects of sAPRIL-BP on tumor development.
<p>LOVO cells were injected subcutaneously into nude mice and allowed to grow for 3 weeks. Once the tumor was establishes, the mice were divided into 3 groups (N = 5) and treated with PBS (control), low (20 mg/kg), or high (40 mg/kg) dose of sAPRIL-BP every other day. (A) Representative examples of the tumors from each group are shown. Top panel: Scale bar, 8 mm. Bottom panel: Scale bar, 7 mm. (B) Mice were sacrificed after two weeks of treatment with sAPRIL-BP and the tumor weights were recorded. *<i>p</i> <0.05 compared to control. #<i>p</i> <0.05 compared to the low dose group. (C) The tumor volume was recorded every two days during treatment. *<i>p</i> <0.05 compared to control.</p
Analysis of the correlation between Th1 cytokines and sBAFF/sAPRIL. A
<p>. The levels of IFN-γ, IL-12p70 and IL-2 were detected in plasma (HD, n = 15; LTB<sub>L</sub>, n = 11; LTB<sub>H</sub>, n = 14; TB, n = 11) and pleural effusion (TP, n = 10) using Luminex technology. <b>B</b>. Significant positive correlations were identified between sAPRIL, and IFN-γ (Pearson’s correlation coefficient, <i>r</i> = 0.8412, <i>p</i> = 0.0023), IL-12p70 (Pearson’s correlation coefficient <i>r</i> = 0.8211, <i>p</i> = 0.0036) and IL-2 (Pearson’s correlation coefficient <i>r</i> = 0.7424, <i>p</i> = 0.0139) in the TP pleural effusion.</p
Effect of sAPRIL-BP on the proliferation of LOVO and SW620 cells.
<p>(A) APRIL<sup>high</sup> LOVO and HCT116 cells and (B) APRIL<sup>low</sup> SW620 and HT-29 cells were treated with the indicated doses of sAPRIL binding peptides for 24, 48, and 72 h, and proliferation was determined using the CCK-8 kit. The rate of proliferation inhibition was calculated as: (%) = [(mean of OD<sub>control</sub>—mean of OD<sub>experimental</sub>) / mean of OD<sub>control</sub>]×100%.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
