The prognostic significance of tumor-infiltrating lymphocytes in cervical cancer / 부인종양

Objective@#To predict the prognosis of cervical cancer, we constructed a novel model with 5 specific cell types and identified a potential biomarker. @*Methods@#We employed CIBERSORT and xCell method to evaluate the abundances of 23 cells types in tumor microenvironment. Five specific cell types were filtrated to determine different immunotypes by applying least absolute shrinkage and selection operator (LASSO) Cox regression method. The expression of immune checkpoints (ICPs) and effectors were validated by immunohistochemistry. Correlation analysis was performed to examine the relevance between PIK3CA mutational status and ICPs. @*Results@#Unsupervised clustering of patients on the basis of tumor infiltrating lymphocytes and fibroblasts identified patients with shorter overall survival (OS) (hazard ratio [HR]=3.0729; 95% confidence interval [CI]=1.5103–6.2522; p=0.0118). An immunoscore (IS) signature consisting of 5 immune cell types infiltrating in tumor core (CD8T, activated NK cells, neutrophils, activated mast cells, macrophages) was constructed using LASSO Cox regression analysis. Receiver operating characteristic curves confirmed that the area under the curve of IS was significantly higher to that of International Federation of Gynecology and Obstetrics staging alone (0.637 vs. 0.55). Survival analysis revealed patients in high IS group exhibited a poorer OS (HR=3.0113; 95% CI=1.8746–4.8373; p<0.0001). The multivariate analysis indicated the IS was an independent prognostic factor. In addition, the lower IS related to higher expression of ICPs and neoantigen load. @*Conclusions@#The identification of IS in cervical cancer tissues could facilitate patient risk stratification and selection of immunotherapeutic responses, but more prospective studies are needed to assess its reliability.

Olaparib induced senescence under P16 or P53 dependent manner in ovarian cancer / 부인종양

OBJECTIVE: Poly (ADP-ribose) polymerase (PARP) is an important molecule in the early stress response of DNA damage, which is involved in DNA damage repair and cellular senescence. Olaparib, as PARP inhibitor, has an anti-tumor effect on high grade serous ovarian cancer, but its effects on cellular senescence have not been reported. This study intends to explore the role of olaparib in the regulation of senescence in ovarian cancer cells. METHODS: The effects of olaparib on the senescence of ovarian cancer cells were detected by using the senescence-associated β-galactosidase (SA-β-Gal) and senescence-associated heterochromatin aggregation (SAHF). Quantitative real-time polymerase chain reaction was used to analyze the senescence-associated secretory phenotype (SASP). Cell cycle and apoptosis were detected by flow cytometry. The effect of olaparib on tumor growth was analyzed in a nude mouse xenograft transplantation model. RESULTS: Long-term (6 days) treatment with olaparib (5 μM) significantly inhibited the growth of ovarian cancer cells, leading to arrest the cell cycle at G0/G1 phase, significant increase the number of positive SA-β-Gal stained cells and positive SAHF cells. The expression of P16 and retinoblastoma protein (p-RB) were significantly enhanced in SKOV3 cells under olaparib treated, meanwhile, the expression of P53 and p-RB were upregulated in A2780 cells. In OVCAR-3 cells, the expression of P53 was downregulated and p-RB was upregulated. Mice with SKOV3 xenograft transplantation was given olaparib (10 mg/kg/day) via abdominal cavity administration, the tumor volume was reduced (p < 0.01). CONCLUSION: Continuous low dosage administration of olaparib induced senescence under P16 or P53 dependent manner in ovarian cancer.

Application of PET-CT in efficacy evaluation of neoadjuvant chemotherapy for breast cancer / 肿瘤研究与临床

Objective To evaluate the value of PET-CT in patients with breast cancer and to determine if the PET-CT can provide additional information to predict early response to neoadjuvant chemotherapy (NAC).Methods NAC was given to 20 patients with breast cancer confirmed by biopsy puncture from September 2009 to March 2012.The PET-CT was carried out for all patients before NAC.TEC program with three weeks for one cycle was selected.After 6 days of the first cycle,the PET-CT was performed again.The changes of standard uptake value before and after the first cycle were compared.At the same time hand palpation was selected to detect the changes in tumor size before and after the first cycle of NAC.The changes of the standard uptake value and in tumor size need to refer to the pathology Miller & Payne classification methods to evaluate the efficacy of the NAC.Results The SUV were (7.51±1.76) Bq/ml and (4.98±1.61) Bq/ml before and after chemotherapy (t =7.916,P ＜ 0.05) the maximum tumor diameters were (9.62±4.38) cm and (8.89±4.08) cm before and after NAC (t =2.154,P＞ 0.05).SUV had highly correlated with pathological MP classification (r =0.725,P =0.000); while for the tumor size there was no significant change (r =0.026,P =0.824).Conclusion PET-CT can predict the efficacy earlier and is more accurate than clinical efficacy standard for the NAC.

The role of hepatic stellate cells SSeCKS expression in liver fibrous / 中华内科杂志

Objective To investigate the change and effect of SSeCKS(src suppressed c kinase substrates)in the activation of hepatic stellate cells(HSCs).Methods HSCs were isolated from normal rats,the change of SSeCKS mRNA expression on HSCs culture in vitro was determined using real.time PCR.protein level was determined by Western blot and immunofluorescence methods.A rat model of liver fibrosis was established.The expression and location of SSeCKS and α-SMA(α-smooth muscle actin)in liver tissues were detected by immunofluorescence methods.Results SSeCKS mRNA expression WaS loW in freshly isolated HSCs cell and the expression increased in activated HSCs in vitro.In liver fibrosis tissue,the number of SSeCKS-positive cells was increased and these cells were distributed along the sinusoids which also contained α-SMA positive cells.Conclusion The expression of SSeCKS was increased in activated HSCs in vitro.Therefore.SSeCKS may be involved in the liver inflammation and fibrosis.

Characterization of the ultrastructure and cytoskeleton of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To explore ultrastructure and cytoskeleton characteristics of bone marrow-deftved mesenchymal stem cells (MSCs) in patients with systemic lupus erythematosus (SLE).Methods MSCs were isolated from bone marrow of 2 SLE patients and 2 healthy controls.Their ultrastrnctures were examined by transmission electron microscope (TEM).The expression pattern of actin and vinculin was assessed by laser confocal microscopy (LCM).Results MSCs in patients with SLE presented with signs of ageing and lots of autophagosome could be found in most of the cells.F-actin was aggregated and condensed at the:border of cytoplasm.Vinculin was arranged disorderly and condensed in the cytoplasm.Conclusion The change of uhrastructure and cytoskeleton patterns of bone marrow derived mesenchymal cells of SLE patients may play an important role in the abnormal proliferation of these cells in vitro.

Effects of LPS and TNF-? on expression of SSeCKS by endothelial cell / 中国免疫学杂志

Objective:To study the effects of LPS and TNF-? on the expression of SSeCKS and morphology as well as cytoskeleton of endothelial cell, so as to explore the role of SSeCKS in cell morphology changes.Methods:The cultured Bovine pulmonary artery endothelial cells(BPAEC) was induced by LPS, TNF-? and the expression of SSeCKS was detected by in situ hybridization,Western blot and immunohistology. Immunofluorescent staining method with confocal laser-scanning fluorescence microscope was used to observe the effects of LPS and TNF-? on the morphology of endothelial cells and the organisation of SSeCKS as well as cytoskeleton.Results:Firstly, we found that TNF-? could induce the expression of SSeCKS in a concentration and time dependent manner , meanwhile LPS had no effects on SSeCKS expression. Secondly, it was observed that LPS and TNF-? induced reorganization of F-actin and SSeCKS in endothelial cell. Thirdly,PKC inhibitor Ro-31-8220 reversed the effect of LPS,TNF-? on F-actin and SSeCKS in endothelial cells.Conclusion:The results demonstrate that TNF-? could induce endothelial cell to express SSeCKS; PKC plays a role in the reorganization of SSeCKS and F-actin in endothelial cells induced by LPS and TNF-?; the results suggest that the mechanism for reorganization of cytoskeleton induced by LPS, TNF-? be partially related to the SSeCKS of ECs.

Moral Conflicts in Current Healthcare Reform and Countermeasures / 中国医学伦理学

This essay probes into the reality,causes and solutions to the moral conflicts in the healthcare reform in current China,aiming to provide reference from an ethical perspective for correctly understanding and solving the problems in current healthcare reform.