ABSTRACT
Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.
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Objective To compare the efficacy and prognosis of epirubicin combined with paclitaxel and epirubicin combined with docetaxel in the treatment of breast cancer.Methods Patients in the study group were treated with epirubicin and paclitaxel, while the control group was treated with epirubicin plus docetaxel.Results The two groups of breast cancer patients by the end of the treatment were valid for 5 years of follow-up, five year survival rate(86.67%)than the control group(68.89%), the study group the recurrence rate(4.44%)than in the control group(15.56%), the data had significant differences(P<0.05).Conclusion The epirubicin is conducive to breast cancer patients for better disease control effect and prognosis than star, paclitaxel combined with chemotherapy.
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Objective To explore the effect of SIRT1 gene silencing on the radiosensitivity of diffuse large B-cell lymphoma (DLBCL) cells.Methods Immunohistochemistry was used to measure the protein expression of SIRT1 in DLBCL tissues.Western blot was used to measure the expression of SIRT1 in DLBCL cell lines (OCI-Ly3,SU-DHL-2,and SU-DHL-4) and the immortalized B cell line HMy2.CIR.After SU-DHL-4 cells were transfected with si-SIRT1 and si-NC using Lipofectamine 2000,the expression of SIRT1 was determined by Western blot.MTT assay and colony-forming assay were used to assess the cell growth and colony formation ability of SU-DHL-4 cells treated with radiation.The group t-test or univariate analysis of variance was used for comparison between groups.Results The expression rate of SIRT1 in DLBCL tissues was 72.6%(103/140),which was significantly higher than that in reactive lymphoid hyperplasia (RLH) tissues (26.5%,8/25)(P=0.001).The SIRT1 expression was significantly higher in DLBCL cells than in HMy2.CIR cells (P=0.020).After SIRT1 gene silencing by si-SIRT1,the expression of SIRT1 was significantly reduced in SU-DHL-4 cells (P=0.008).Besides,SIRT1 gene silencing significantly reduced the growth rate and colony formation ability of SU-DHL-4 cells treated with radiation (P=0.030).Conclusions SIRT1 gene silencing enhances the radiosensitivity of DLBCL cells,providing a novel target for the radiotherapy of DLBCL.
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Objective To investigate the effect of Avastin (bevacizumab) combined with preoperative FOLFOX neoadjuvant chemotherapy on the prognosis of patients with locally advanced rectal cancer (LARC).MethodsA total of 80 cases of patients with LARC treated with total mesorectal excision (TME) in our hospital from January 2013 to January 2016 were randomly divided into the control group and the observation group, 40 cases in each group.The control group were treated with preoperative FOLFOX chemotherapy while the observation group were treated with bevacizumab injection, based on the treatment in the control group.21 days was a cycle of chemotherapy, and both groups were treated for at least 4 cycles.After 6 cycles of chemotherapy, operation was carried out, following TEM principle.The short-term and long-term prognosis, rate of R0 resection, the incidence of postoperative complications and side effects of chemotherapy were compared between the two groups.ResultsThere was no significant difference between the two groups in the good response rate of chemotherapy, the rate of R0 resection, the incidence of postoperative complications, the 1-year and 3-year survival rates and 1-year disease-free survival rate.The incidence rates of gastrointestinal reactions and bone marrow suppression in the observation group were 52.5% and 52.5%, respectively while in the control group were 25.0% and 20.0%, respectively (P<0.05), but there was no significant difference in the incidence rates of grade Ⅲ~Ⅳ gastrointestinal reaction and bone marrow suppression between the observation group and the control group (5.0% and 15.0% vs 2.5% and 5.0%).The 3-year disease-free survival rate of the observation group was higher than that of the control group (82.5% vs 60.0%) (P<0.05).ConclusionThe application of bevacizumab combined with preoperative FOLFOX chemotherapy in the treatment of LARC can improve the 3-year disease-free survival rate, without increasing postoperative adverse reactions and serious side effects of chemotherapy.
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The stable quality of Chinese herbal medicines is a critical factor for their reliable clinical efficiency. An improved liquid-liquid extraction procedure and a liquid chromatographic method were developed to simultaneously analyze five anthraquinones (aloe-emodin, rhein, emodin, chrysophanol and physcion) in a Chinese traditional hospital preparation, Fuyankang mixture, in order to quantitatively control its quality in a more effective way.