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Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.
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On the basis of relevant literature, according to the clinical experience of Tuina specialists, a preliminary plan of Tuina for nonspecific low back pain has been formed. An expert consensus meeting was used to form a non-specific low back pain assessment program and 3 modern Gongting Lijinshu (Tuina massage) for the treatment of nonspecific low back pain. The treatment has showed to be clinically repeatable and suitable for the RCT study.
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A series of triazole derivatives were designed and synthesized based on a natural product cembrane separated from Croton laevigatus Vahl which showed potential antitumor activity against HeLa cells.Twelve novel compounds were synthesized and their structures were characterized by 1H NMR, 13C NMR and HRMS.Their cytotoxicities in vitro were evaluated for HeLa,K562 and K562/A02 cells by MTT assay.The results showed that some cembrane derivatives possessed antitumor activities.Substituted triazole connected to cembrane derivatives exhibited potent activity toward drug-resistant K562/A02 cells.
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Objective To investigate the expression of androgen receptor(AR),ATAD2 in hepatocellular carcinoma(HCC) and the correlations with clinicopathological features,and the role of DHT/AR and ATAD2 in proliferation of HCC cells.Methods The samples of 75 patients with HCC in the First Affiliated Hospital of China Medical University from February 2012 to December 2012 were collected.LM3 and Huh7 cells were divided into control group,DHT group,DHT + CDX (bicalutamide) group and CDX group;and also divided into Ri-ATAD2 group (adding interference fragments) and Ri-C group (adding control vector sequence).Immunohistochemistry was used to detect the expression of AR and ATAD2,and to analyze the correlations between clinical features and survival of patients.Real-time PCR and Western Blot were used to detect the expression of AR and ATAD2,and CCK-8 was used to detect cell proliferation.Results HCC patient samples were grouped according to AR and ATAD2 expression.Compared with low AR expression group (n =31),the ratio of tumor ＜5 cm in high expression group (n =44) was higher,and the ratio of TNM stage Ⅰ + Ⅱ was lower.Compared with low ATAD2 expression group (n=35),the ratio of metastasis and tumor differentiation grade Ⅲ + Ⅳ was higher in high expression group (n=40),and the difference was statistically significant (P ＜ 0.05).The overall survival rate of patients with high expression of ATAD2 was lower than other patients,and the differences were statistically significant (P＜0.05).Multivariate Cox regression analysis showed that ATAD2 expression (HR=1.935,95％ CI:1.066～3.515) and metastasis (HR=2.212,95％ CI:1.059～4.619) were independent predictors of poor prognosis.Compared with LO2 cells,the mRNA and protein level of AR and ATAD2 in LM3 and Huh7 cells were significantly higher,and the differences were statistically significant (P＜0.05).And the proliferation rate of HCC cells increased significantly after 48 and 72 hours compared with the control group,and the differences were statistically significant (P＜0.05).After adding CDX,the proliferation of LM3 and Huh7 induced by DHT was inhibited.DHT enhanced the expression of ATAD2,while CDX inhibited the expression of ATAD2.The expression of ATAD2 protein decreased when LM3 and Huh7 cells were interfered.Compared with Ri-C group,the proliferation of HCC cells in Ri-ATAD2 group decreased significantly after the DHT treatment 48 and 72 hours,and the difference was statistically significant (P＜0.05).Conclusions DHT/AR promoted the proliferation of HCC cells by inducing ATAD2 expression.Modulating ATAD2 expression may be the potential mechanism of DHT/AR in HCC proliferation.
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Objective To investigate in vivo pharmacokinetics and bioequivalence of Meloxicam Chewable Tablets in healthy Beagle's dogs.Method Twelve healthy adult Beagle's dogs were randomized into two groups.Using the double-preparation,double-cycle,cross-over method and administering orally of testing and reference tablet (2 mg) respectively.The plasma concentration of meloxicam was determinated by RP-HPLC.The 3P97 software was adopted to calculate the pharmacokinetic parameters and evaluate the bioequivalence of two preparations.Results The area under the curves (AUC0-96 h) of the testing tablets and innovator tablets were (2.85±0.64) and (2.79±0.48) μg/mL·h.The peak time (Tmax) was (4.33±0.65) and (4.16±0.71) h.The peak concentration (Cmax) was (0.091±0.017) and (0.086±0.021) μg/mL.The half time (t1/2) was (26.08±3.64) and (26.94± 4.21) h.After the double unilateral t test,there was no statistical significance in the difference of lnAUC and lnCmax between the testing tablets and innovator tablets.Conclusion The testing tablets and innovator tablets are bioequivalent.The relative bioavailability of generic tablet is (98.0±9.76)％.
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Castleman's disease is a rare disorder of the lymphoid system characterized by noncancerous growths that may develop in lymph node tissues throughout the body. The incidence of this disease has been increasing in recent years. Because of the difficulty of diagnosis and high-misdiagnosis, more and more clinicians have paid close attention to this disease. By the clinical work, and with the help of related reports, the preliminary summary of this disease is made.
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Microtubule is one of the key components of the cytoskeleton and plays an important role in the maintenance of cell shape and the process of signal transduction and mitosis. Due to the extreme importance of microtubule in the process of mitosis, tubulin becomes one of the most important targets for development of new anticancer drugs and tubulin inhibitors are used for the treatment of cancer nowadays. These inhibitors have antitumor activity by inhibiting or promoting the assembly of tubulin to microtubules and interfering the process of cell mitosis. This review summarized the research progress of the tubulin inhibitors, especially the introduction of the tubulin inhibitors of pharmacological activities and the progress of clinical research. Also, the development trend of these inhibitors is discussed.
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Microtubule is one of the key components of the cytoskeleton and plays an important role in the maintenance of cell shape and the process of signal transduction and mitosis. Due to the extreme importance of microtubule in the process of mitosis, tubulin becomes one of the most important targets for development of new anticancer drugs and tubulin inhibitors are used for the treatment of cancer nowadays. These inhibitors have antitumor activity by inhibiting or promoting the assembly of tubulin to microtubules and interfering the process of cell mitosis. This review summarized the research progress of the tubulin inhibitors, especially the introduction of the tubulin inhibitors of pharmacological activities and the progress of clinical research. Also, the development trend of these inhibitors is discussed.
Subject(s)
Humans , Antineoplastic Agents , Chemistry , Pharmacology , Microtubules , Metabolism , Mitosis , Molecular Structure , Neoplasms , Drug Therapy , Stilbenes , Chemistry , Pharmacology , Structure-Activity Relationship , Tubulin , Metabolism , Tubulin Modulators , Chemistry , PharmacologyABSTRACT
Objective:To construct a phage display antibody library of special antigen responding to serum starved U251 cell,from which the serum responding gene and protein would be gotten.Methods:U251 cells were cultured in serum-absent midium for 48 h.Its protein was extracted and used to immunize BALB/c mice.Total RNA of the spleenocytes of immunized mice was extracted.VH and VL were amplified by RT-PCR and were linked into ScFv(Single chain fragment of variation) with a linker.ScFv was recombined to pCANTAB5E vector and was transformed to TG1 strain.Results:The library capacity was up to 3?106 cfu/L.A positive clone was identified from 8 random clones of this library.Conclusion:The special ScFv phage library is constructed successfully.It is the basis for screening special antibodies which can recognize serum responding protein.