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Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm that was recently reported to exhibit recurrent NCOA1-3rearrangement with the most frequent partners ESR1 and GREB1. In this study, the clinicopathological characteristics of 17 UTROSCT cases were summarized; among them, the fusion genes of 12 cases were retrospectively analyzed by targeted RNA sequencing. The mean age of our cohort was 47 years (19-67 y). Although the majority of UTROSCTs had clear boundaries on gross examination, microscopic infiltration into the myometrium was observed in 82.4 % of cases. The tumor cells showed diffuse, trabecular, nested, reticular, pseudopapillary, hollow and solid tubular patterns, expressing sex cord, epithelial, and myogenic markers. Six fusion genes, including ESR1::NCOA3 (n = 4), ESR1::NCOA2 (n = 2), ESR1::CITED2 (n = 2), GREB1::NCOA2 (n = 2), GREB1::NCOA1 (n = 1), and GREB1::NCOA3 (n = 1), were identified. The fusion genes of the three cases with recurrence and metastasis were GREB1::NCOA2, ESR1::NCOA3, and ESR1::CITED2. All 3 cases of recurrent tumors showed infiltrative growth, with moderate to severe dysplasia of tumor cells and different degrees of rhabdomyoid differentiation. This is the first report of the ESR1::CITED2 fusion genes in UTROSCT, and one of the two patients had recurrence and metastasis. Compared with UTROSCT withESR1 rearrangement, UTROSCT with GREB1 rearrangement was more common in elderly patientsand was more likely to present with intramural masses, less sex cord differentiation, poor prognosis, and relapse and metastasis.
Subject(s)
Ovarian Neoplasms , Sex Cord-Gonadal Stromal Tumors , Uterine Neoplasms , Female , Humans , Aged , Middle Aged , Retrospective Studies , Neoplasm Recurrence, Local/genetics , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology , Sex Cord-Gonadal Stromal Tumors/genetics , Sex Cord-Gonadal Stromal Tumors/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Molecular Biology , Repressor Proteins , Trans-ActivatorsABSTRACT
Metabolic regulation has been proven to play a critical role in T cell antitumor immunity. However, cholesterol metabolism as a key component of this regulation remains largely unexplored. Herein, we found that the low-density lipoprotein receptor (LDLR), which has been previously identified as a transporter for cholesterol, plays a pivotal role in regulating CD8
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Objective To use in vitro experiments to verify the changes of proliferation, senescence and apoptosis of hepatocellular carcinoma cells after inhibiting the expression of NEK7, and to explore the related molecular mechanism. Methods Western blot and RT-PCR were used to detect the expression of NEK7 in hepatocellular carcinoma cells and THLE-2 cells. A viral vector was designed to inhibit the expression of NEK7 based on the gene sequence. After hepatocellular carcinoma cells were transfected, we observed the changes of proliferation activity, cell senescence, cell apoptosis and cell cycle in vitro. Western blot was used to detect the expression of cell cycle-related factors. Results Compared with THLE-2 cells, NEK7 was highly expressed in hepatocellular carcinoma cells. After inhibiting the expression of NEK7 with shRNA, the proliferation of hepatocellular carcinoma cells was inhibited, the proportions of cell senescence and apoptosis were increased, meanwhile, the cell number in stage S and G2/M was significantly reduced, the cell cycle progression was blocked, the expression levels of C-myc, c-Fos, cyclin D1 and cyclin E were inhibited, P16 and P27 expression were increased, and CDK2, CDK4 and CDK6 expression were not significantly changed. Conclusion After inhibiting the expression of NEK7, the proliferation ability of hepatocellular carcinoma cells is reduced, cell senescence is promoted and apoptosis is induced; meanwhile, the cell cycle progress is blocked.
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Toxoplasma gondii is an obligatory intracellular parasite that critically depends on active invasion and egress from infected host cells to complete its propagation cycle. T. gondii rhoptry proteins (TgROPs) are virulent factors associated with host cell invasion, growth. In this study, we analyzed the functions of ROP9 in the process of T. gondii infection. The TgROP9 knockout RH strain (RHâ³ROP9) and its recovery strain (RH-ReROP9) were constructed using the CRISPR/Cas9 system. The invasion, proliferation, and egress efficiency of the RHâ³ROP9 strain were evaluated and their pathogenicity to mice was analyzed. Compared with RH wild-type (RH-WT) and RH-ReROP9 strains, the invasion percentage of RHâ³ROP9 to Vero cells was reduced by about 28.0% (p< 0.01) at 1.5 h, and the relative proliferation percentage was decreased by about 35.0% (p< 0.01) after infection with 102 or 103 parasites. In addition, the RHâ³ROP9 strain also showed prolonged egress time from host cells. The survival time of the mice (12.6 ± 1.6 or 10.1 ± 1.1 days) were delayed (p < 0.001) after infection with either 200 or 1000 RHâ³ROP9 parasites. These evidences suggested that ROP9 facilitated T. gondii infection in vitro and in vivo.
Subject(s)
Antigens, Protozoan/physiology , Membrane Proteins/physiology , Toxoplasma/pathogenicity , Animals , Chlorocebus aethiops , Female , Mice , Mice, Inbred BALB C , Vero CellsABSTRACT
Dengue virus (DENV) is the most widely transmitted arbovirus in the world. Due to the lack of diagnostic technology to quickly identify the virus serotypes in patients, severe dengue hemorrhagic fever cases caused by repeated infections remain high. To realize the rapid differential diagnosis of different serotypes of DENV infection by immunological methods, in this study, four DENV serotype NS1 proteins were expressed and purified in mammalian cells. Monoclonal antibodies (MAbs) against NS1 protein were obtained by hybridoma technology after immunizing BALB/c mice. Enzyme-linked immunosorbent assay, indirect immunofluorescence assay, dot blotting, and Western blotting were used to confirm the reactivity of MAbs to viral native NS1 and recombinant NS1 protein. These MAbs include not only the universal antibodies that recognize all DENV 1-4 serotype NS1, but also serotype-specific antibodies against DENV-1, DENV-2 and DENV-4. Double antibody sandwich ELISA was established based on these antibodies, which can be used to achieve rapid differential diagnosis of serotypes of DENV infection. Preparation of DENV serotype-specific MAbs and establishment of an ELISA technology for identifying DENV serotypes has laid the foundation for the rapid diagnosis of DENV clinical infection.
Subject(s)
Animals , Humans , Mice , Antibodies, Monoclonal , Antibodies, Viral/metabolism , Dengue/diagnosis , Dengue Virus/immunology , Enzyme-Linked Immunosorbent Assay , Mice, Inbred BALB C , Sensitivity and Specificity , Serogroup , Viral Nonstructural Proteins/immunologyABSTRACT
Objective:To investigate the serum expression of long non-coding RNA overlapping transcription content KCNQ1OT1 (KCNQ1) gene in patients with coronary artery disease (CAD) and its clinical significance. Methods:A total of 196 patients treated in our hospital were divided into 2 groups:CAD group and Control group, the patients were without CAD. n=98 in each group. Expression levels of serum KCNQ1OT1 and P53 were measured by quantitative RT-PCR;the relationship between KCNQ1OT1, P53 and clinical features in relevant patients were analyzed. Results:Compared with Control group, CAD group had increased expression of serum KCNQ1OT1 and decreased expression of P53, both P Conclusion:CAD patients had obviously increased serum level of KCNQ1OT1;KCNQ1OT1 was independently related to CAD occurrence.
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Objective To establish a mouse model by transplanting subcutaneously human pancreatic cancer tissue fragments.Methods Surgically resected pancreatic cancer tissue fragments from patients were transplanted into NOD/SCID mice subcutaneously,and then the growth of the tumor and transplanting it into the next generation were observed.The growth rate,HE staining and immunohistochemistry staining of Ki67 and VEGF were compared.Results We have obtained 13 cases ofpancreatic cancer tissues and 6 cases of biopsy specimens.In 5 cases transplantation was successful,in onemouse model passing to fourth generation,in 4 models to second generation.With the increase of generaions,tumor growth accelerated.HE staining showed later passage cells behavior in an identical manner as the primary cells.Immunohistochemistry staining showed that expressions of Ki67 and VEGF are increasing.Conclusions Through transplanting human pancreatic cancer tissue fragments directly,we have constructed mouse model of pancreatic cancer successfully.With the passage of subculture,the malignant degree and invasiveness may increase.
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OBJECTIVE:To explore the establishment of performance indicator system for evaluating national essential drug system in China.METHODS:Reference to the field of health policy performance evaluation research and practice at home and abroad.WHO indicators for evaluating national drug policies,and a qualitative study on the theory and approach of policy evaluation was conducted.RESULTS & CONCLUSION:To establish a China-specific performance evaluation indicator system,policy goals should be specified,and evaluation criterions and policy components should be also defined firstly.An indicator system framework of national essential drug system which based on WHO recommendatory indicators should be proposed accordingly.But detailed indicators should be established based on field research and experts counseling.
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OBJECTIVE:To provide references for the establishment of performance indicator system for evaluating National essential medicines system in China. METHODS:To analyze the theory and approach of policy evaluation and WHO indicators for evaluating national drug policies. A literature study on relevant information was conducted. RESULTS & CONCLUSION:China may refer to WHO framework for the evaluation index system,according to the target of various stages of essential drugs system,in the implementation of our system of essential medicines on the basis of a full investigation,combined with our medical and health background and status,build essential drugs system of performance appraisal system and performance indicators.
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This article reviews the recent achievements in parasitology including new diagnostic techniques,molecular mechanism of parasitic pathogenesis,drug resistance,antigenic variation,parasite genomics and proteomics. The perspective development in the area is also discussed.