A systematic review of anti-interleukin-17 antibody in the treatment of plaque psoriasis / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of anti-interleukin-17 antibody in the treatment of plaque psoriasis.</p><p><b>METHDOS</b>Randomized controlled trials (RCT) of anti-interleukin-17 antibody (Secukinumab, Brodalumab, and Ixekizumab) in the treatment of plaque psoriasis published between January, 2000 and March, 2017 were searched from PubMed, Cochrane Library, EBSCO, EMbase, CBM, CNKI, VIPdetabase, and Wangfang database. The quality of the retrieved trials was evaluated and the results of studies were analyzed using RevMan 5.0 software.</p><p><b>RESULTS</b>Thirteen RCTs were included involving a total of 11 203 patients. Meta-analysis showed a significant differences between anti-interleukin-17 antibody and placebo (or positive drug) in terms of PASI75 and sPGA (P<0.05). The total incidence of adverse events differed significantly between anti- interleukin-17 antibody and placebo, but no significant differences were found between them in the incidence of serious adverse events and discontinuation rate due to adverse events (P>0.05).</p><p><b>CONCLUSION</b>Anti-interleukin-17 antibody is safe and effective for treatment of plaque psoriasis.</p>

Mechanism of miR-21 via Wnt/β-catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice

OBJECTIVE@#To study the mechanism of effect of miR-21 via Wnt/β-catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice.@*METHODS@#The effect of miR-21 on A549 cells were detected by MTT method. MiR-21 expression levels were overexpressed or inhibited in A549 cells by transfecting with miR-21 mimics or inhibitors. Correlation among key molecules (Wnt1, β-catenin, CyclinD1 and miR-21) of mRNA and protein levels in Wnt/β-catenin signaling pathway were studied by Real-time PCR and Western blot hybridization assay. Invasive ability of A549 cells was determined via Transwell chamber cell invasion assay; the role of miR-21 in A549 cells was explored via the Wnt/β-catenin signaling pathway. A Lewis lung carcinoma animal model was established to detect miR-21 expressions in tumor animals and controlled animal tissues, and verify expression changes of the above molecules in the Wnt/β-catenin signaling pathway was determined in the animal level.@*RESULTS@#MTT assay results showed that miR-21 overexpression could markedly enhance cell absorbance value; that is, miR-21 could increase the ability proliferation of A549 cells. β-catenin and CyclinD1 expression levels were significantly higher in miR-21 mimic transfected cells (P < 0.05), and Wnt1 gene had no significant change. Wnt1, β-catenin and CyclinD1 gene expression showed no significant change when miR-21 expression was suppressed, compared with controls. After cells were transfected with miR-21 mimics, cell invasion assay revealed that the perforated cells was significantly higher than the perforated cells in the control group (P < 0.01). Lewis lung assay revealed that miR-21 expression levels in the Lewis lung carcinoma were significantly higher; and at the same time, Wnt1, β-catenin and CyclinD1 gene expression levels were significantly increased, compared to controls.@*CONCLUSIONS@#In A549 human lung cancer cells and Lewis lung carcinoma in mice, key molecules β-catenin and CyclinD1of miR-21 expressions and the Wnt/β-catenin signaling pathway are positively correlated.

Mechanism of miR-21 via Wnt/β-catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice

Objective: To study the mechanism of effect of miR-21 via Wnt/β-catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice. Methods: The effect of miR-21 on A549 cells were detected by MTT method. MiR-21 expression levels were overexpressed or inhibited in A549 cells by transfecting with miR-21 mimics or inhibitors. Correlation among key molecules (Wnt1, β-catenin, CyclinD1 and miR-21) of mRNA and protein levels in Wnt/β-catenin signaling pathway were studied by Real-time PCR and Western blot hybridization assay. Invasive ability of A549 cells was determined via Transwell chamber cell invasion assay; the role of miR-21 in A549 cells was explored via the Wnt/β-catenin signaling pathway. A Lewis lung carcinoma animal model was established to detect miR-21 expressions in tumor animals and controlled animal tissues, and verify expression changes of the above molecules in the Wnt/β-catenin signaling pathway was determined in the animal level. Results: MTT assay results showed that miR-21 overexpression could markedly enhance cell absorbance value; that is, miR-21 could increase the ability proliferation of A549 cells. β-catenin and CyclinD1 expression levels were significantly higher in miR-21 mimic transfected cells (. P<0.05), and Wnt1 gene had no significant change. Wnt1, β-catenin and CyclinD1 gene expression showed no significant change when miR-21 expression was suppressed, compared with controls. After cells were transfected with miR-21 mimics, cell invasion assay revealed that the perforated cells was significantly higher than the perforated cells in the control group (. P<0.01). Lewis lung assay revealed that miR-21 expression levels in the Lewis lung carcinoma were significantly higher; and at the same time, Wnt1, β-catenin and CyclinD1 gene expression levels were significantly increased, compared to controls. Conclusions: In A549 human lung cancer cells and Lewis lung carcinoma in mice, key molecules β-catenin and CyclinD1of miR-21 expressions and the Wnt/β-catenin signaling pathway are positively correlated.

Effect of YM155 on Apoptosis and Autophagy of K562 Cells / 中国实验血液学杂志

<p><b>OBJECTIVE</b>This study was purposed to investigate the effect of YM155, a survivin inhibitor, on the apoptosis and autophagy of K562 cells.</p><p><b>METHODS</b>K562 cells were treated with YM155 at different concentration. Cell survival was analyzed by CCK-8 assay, the cell apoptosis was detected by flow cytometry. Survivin, BCL-2 and beclin1 mRNA expressions were determined by RT-PCR. Survivin, BCL-2, caspase-3, PARP and LC-3 protein expressions were assayed by Western blot.</p><p><b>RESULTS</b>YM155 inhibited the proliferation of K562 cells in a time- and dose-dependent manners. With the increasing of YM155 concentration and prolonging of action time, the expression levels of mRNA and protein of survivin and BCL-2 decreased, while the expression levels of caspase-3, PARP, beclin1 and LC-3 increased. Compared with the YM155 group, the protein levels of LC-3 and caspase-3 were lower in YM155 combined with 3-MA group.</p><p><b>CONCLUSION</b>YM155 can inhibit K562 cell proliferation by inducing apoptosis and autophagy, while autophagy induction effect can enhance its cytotoxic effect.</p>

Immune response of recombinant IFN-α-2b-BCG treatment in mice bladder cancer / 中华泌尿外科杂志

Objective To study local and systemic immune response in an animal model treated with recombinant hIFN-α-2b-BCG instillation. Methods The MB49 orthotopic bladder cancer model in C57BL/6 mice was established and treated separately with rBCG, wild BCG, wild BCG combined with IFN-α-2b and PBS as the control. The changes of lymphocyte subgroups in peripheral blood were analyzed with FCM, and mTNF-α and mIL-12 in peripheral blood of mice were detected with ELISA.Immunohistochemistry was carried out to detect the local immune reaction, T cell subsets and FAS, in bladder cancer after being treated with rBCG or wBCG. Results The content of CD4+ T lymphocyte was up-regulated in the rBCG group. The CD4+/CD8+ ratio of 2. 63 was up-regulated than pretreatment, significantly different than that of wBCG group(P＜0.05). ELISA assay showed that BCG significantly up-regulated the level of mTNF-α and mIL-12 in serum of orthotopie murine bladder cancer mice. The mTNF-α 806 pg/ml, mIL-12 860 pg/ml in rBCG group, was not significantly higher than those in wBCG group and combination group. The immunocompetent cell numbers with CD3, CD4,CD8 phenotype increased significantly in the tumor tissue of BCG treated group than the control(P＜0.05). The results of CD4+ in rBCG group and the combination group, and CD8+ in rBCG group were significantly higher than that of the wBCG(P＜0.05). The expression of Fas in tumor tissues treated with intravesical BCG was increased(P＜0. 05). Conclusions The recombinant IFN-α-2b-BCG can retrieve the disproportion of systemic lymphocyte subgroups, and increases Th1-type factors and local Fas expression in orthotopic murine bladder cancer. The recombinant IFN-α-2b-BCG is effective in regulating local and systemic immune reaction in orthotopic murine bladder cancer model.

Effect of recombinant hIFN-alpha-2b-BCG on mouse bladder tumor MB49 cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the antitumor effect of recombinant IFN-alpha-2b-BCG on mouse bladder cancer MB49 cells in vitro, and to explore its antitumor mechanisms.</p><p><b>METHODS</b>MB49 cells were co-cultured with recombinant BCG or wild BCG, and than were examined by light and transmission electron microscopy. The cell growth was assessed by MTT assay, and apoptosis rate and MHC-I of the MB49 cells was detected by flow cytometry using AO and Hoechst33258 fluorescence immunostaining.</p><p><b>RESULTS</b>The hIFN-alpha-2b-BCG-treated tumor cells showed slow growth, detachment of some cells, and various degree of degeneration. Light microscopy revealed organelle disorganization, chromatin aggregation, nuclear pyknosis, and cytolysis in some cells. Cellular membrane bulged and some bubbles were seen under fluorescence microscope using AO staining. Hoechst33258 assay also depicted frequent apoptosis in the tumor cells. The MTT assay showed that rBCG more actively than the wild BCG inhibited the proliferation of MB49 cells. The apoptosis rate of the recombinant BCG group was 19.7% and 46.6% at the time point of 24 h and 48 h, respectively, significantly higher than 10.8% and 20.9%, respectively, in the wild BCG group. The results of flow cytometry indicated that both types of BCG enhanced the expression of MHC-I in the MB49 cells, but more effective in the recombinant BCG group.</p><p><b>CONCLUSION</b>The recombinant hIFN-alpha-2b-BCG has more strong immuno-modulatory properties, anti-tumor effect on MB49 cells and induces apparent cytotoxicity in the bladder cancer cells in vitro.</p>

Genetic study of a large Chinese kindred with von Hippel-Lindau disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Von Hippel-Lindau (VHL) disease is a heraditary cancer syndrome caused by germline mutations of the VHL tumor on the suppressor gene. This study was to show the clinical characteristics of a large Chinese kindred with von Hippel-Lindau disease and to evaluate the role of the genetic test of VHL disease in the diagnosis of VHL disease and clinical screening of members of the VHL disease family.</p><p><b>METHODS</b>DNA extracted from peripheral blood was amplified by PCR to three exons of the VHL gene in 27 members of a large kindred with VHL disease. PCR products were directly sequenced. The involvements of multi-organs in the kindred with VHL disease were confirmed by history taking and radiography.</p><p><b>RESULTS</b>Of 47 members in the four generations of the kindred, 18 members were diagnosed as having VHL disease. Clinical manifestations of 18 patients included: central nervous system (CNS) hemangioblastoma (5), renal cell carcinoma and CNS hemangioblastoma (3), renal cell carcinoma and retinal angioma (3), renal cell carcinoma and multiple pancreatic cysts (1), renal cell carcinoma and retinal angioma and multiple pancreatic cysts (2), renal cell carcinoma and CNS hemangioblastomas and multiple pancreatic cysts (1), and multiple pancreatic cysts and multiple renal cysts (1), multiple pancreatic cysts (2). The common lesions of the 18 patients were renal cell carcinoma (55.6%), CNS hemangioblastoma (50.0%), retinal angioma (27.8%), and multiple pancreatic cysts (38.9%). Among the 27 members who volunteered for genetic analysis, 15 members including 9 affected family patients and 2 asymptomatic patients and 4 carriers, who are still alive, presented a codon 78 from Asn to Ser change at nucleotide 446 (A-->G) in exon 1. Four members were carriers with the same VHL gene mutation. Two asymptomatic patients were initially diagnosed by genetic testing and subsequently confirmed radiologically and surgically. Members without gene mutation had no clinical evidence of VHL disease.</p><p><b>CONCLUSIONS</b>The large Chinese kindred with VHL disease was classified as type I. The main characteristics in the kindred were higher incidence of renal cell carcinoma and lower incidence of retinal angioma. Genetic test plays an important role in early detecting asymptomatic patients and the carriers in clinical screening of members of the families with VHL disease. It is also important to prevent the transmission of VHL disease to their offsprings in the kindred.</p>

Familial and genetic study in a large Chinese kindred with von Hippel-Lindau disease and gene mutation analysis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To report the clinical characterization of a large Chinese kindred with von Hippel-Lindau (VHL) disease and to evaluate the role of VHL genetic testing in diagnosis of VHL disease and clinical screening for members in VHL disease family.</p><p><b>METHODS</b>A large kindred with VHL disease was studied. DNA extracted from peripheral blood was amplified by PCR to three exons of VHL gene in 27 members. PCR products were directly sequenced. The data on involvement of multi-organs in the VHL disease kindred were obtained by medical history taking and radiography.</p><p><b>RESULTS</b>There were 47 members in the four generations of the Chinese VHL kindred; among them, 18 members were patients with diagnostically proven VHL disease. Their clinical manifestations included: central nervous system(CNS) hemangioblastoma (n=5), renal cell carcinomas and CNS hemangioblastoma (n=3), renal cell carcinomas and retinal angiomas (n=3), renal cell carcinomas and multiple pancreatic cysts (n=1), renal cell carcinomas and retinal angiomas and multiple pancreatic cysts (n=2), renal cell carcinomas and CNS hemangioblastomas and multiple pancreatic cysts (n=1), and multiple pancreatic cysts and multiple renal cysts (n=1), and multiple pancreatic cysts (n=2). The common lesions of 18 patients in the large kindred were: renal cell carcinomas (56%), CNS hemangioblastomas(50%),retinal angiomas(28%), and multiple pancreatic cysts(39%). Of the 27 members who volunteered for genetic analysis, all 11 affected family patients who are still alive, including 9 affected family patients and 2 asymptomatic patients, presented a codon 78 from Asn to Ser change at nucleotide 446(A to G) in exon 1. Four members were carriers with the same VHL gene mutation. Two asymptomatic cases were initially diagnosed by genetic testing and subsequently confirmed by radiological imaging and surgery. Members not having the gene mutation had no clinical evidence of VHL disease.</p><p><b>CONCLUSION</b>The large Chinese kindred with VHL disease was classified as type . The main characteristics of the kindred are higher incidence of renal cell carcinomas and lower incidence of retinal angiomas. The genetic testing played an important role in early detecting asymptomatic patients and the carriers in clinical screening for members in the VHL families. Also, it is important to prevent the transmission of VHL disease to the offspring in the kindred.</p>