The objective of current study was to develop and validate comprehensive nomograms for predicting the survival of young women with breast cancer.Women aged <40 years diagnosed with invasive breast cancer between 1990 and 2010 were selected from the Surveillance, Epidemiology, and End Results database and randomly divided into training (n = 12,465) and validation (n = 12,424) cohorts. A competing-risks model was used to estimate the probability of breast cancer-specific survival (BCSS). We identified and integrated significant prognostic factors for overall survival (OS) and BCSS to construct nomograms. The performance of the nomograms was assessed with respect to calibration, discrimination, and risk group stratification.The entire cohort comprised 24,889 patients. The 5- and 10-year probabilities of breast cancer-specific mortality were 11.6% and 20.5%, respectively. Eight independent prognostic factors for both OS and BCSS were identified and integrated for the construction of the nomograms. The calibration curves showed optimal agreement between the predicted and observed probabilities. The C-indexes of the nomograms in the training cohort were higher than those of the TNM staging system for predicting OS (0.724 vs 0.694; P < .001) and BCSS (0.733 vs 0.702; P < .001). Additionally, significant differences in survival were observed in patients stratified into different risk groups within respective TNM categories.We developed and validated novel nomograms that can accurately predict OS and BCSS in young women with breast cancer. These nomograms may help clinicians in making decisions on an individualized basis.
Abstract Background: Breast cancer is a common diagnosed malignancy and the leading cause of cancer-related death worldwide. Data on burden and changing trends of breast cancer are of value for policymaking. We therefore aimed to determine the pattern of breast cancer incidence, mortality, and disability-adjusted life-years (DALYs), as well as temporal trends, from 1990 to 2017. Methods: We collected detailed information on breast cancer between 1990 and 2017 using the results of the Global Burden of Disease study in 2017. The number of incident cases, deaths and DALYs attributable to breast cancer are reported as well as age standardized rates. Estimated annual percentage changes (EAPCs) in breast cancer age standardized rate were calculated to quantify the temporal trends. Moreover, attributable burden to breast cancer risk factors were also estimated using the comparative risk assessment framework of the GBD study. Results: There were 878,686 incident cases and 349,581 deaths of breast cancer globally in 2017, contributing to 17,708,600 DALYs. The age standardized incidence rate increased between 1990 and 2017, while the age standardized mortality rate and DALY rate decreased. The corresponding EAPCs were 0.41 (95% CI: 0.35 to 0.47), -0.62 (95% CI: -0.68 to -0.55), -0.56 (95% CI: -0.63 to -0.48), respectively. These trends were heterogeneous across regions and countries. The increase in the age standardized incidence rate was more prominent in countries with a low socio-demographic index and the decrease in the age standardized mortality rate and DALY rate was more prominent in countries with a high socio-demographic index. Percentage of breast cancer deaths due to alcohol use (12.94% to 9.64%) and tobacco (7.15% to 5.14%) was decreasing while deaths due to high body-mass index (4.03% to 6.54%) and high fasting plasma glucose (5.94% to 7.26%) was increasing. Conclusion: Breast cancer remains a major public health concern globally. The trends of incidence, mortality, and DALYs were heterogeneous across regions and countries, suggesting that the allocation of appropriate health care resources for breast cancer prevention, screening and treatment should be considered. Citation Format: Yue Gong, Peng Ji, Xin Hu, Zhi-Ming Shao. The burden and trends of breast cancer from 1990 to 2017 at the global, regional, and national level: Results from the global burden of disease study 2017 [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-08-16.
Abstract Targeting nucleotide metabolism can not only inhibit tumor initiation and progression but also exert serious side effects. With in-depth studies of nucleotide metabolism, our understanding of nucleotide metabolism in tumors has revealed their non-proliferative effects on immune escape, indicating the potential effectiveness of nucleotide antimetabolites for enhancing immunotherapy. A growing body of evidence now supports the concept that targeting nucleotide metabolism can increase the antitumor immune response by (1) activating host immune systems via maintaining the concentrations of several important metabolites, such as adenosine and ATP, (2) promoting immunogenicity caused by increased mutability and genomic instability by disrupting the purine and pyrimidine pool, and (3) releasing nucleoside analogs via microbes to regulate immunity. Therapeutic approaches targeting nucleotide metabolism combined with immunotherapy have achieved exciting success in preclinical animal models. Here, we review how dysregulated nucleotide metabolism can promote tumor growth and interact with the host immune system, and we provide future insights into targeting nucleotide metabolism for immunotherapeutic treatment of various malignancies.
Abstract Background: Metastasis is the main death reason for triple-negative breast cancer (TNBC). Thus, identifying the driving genes associated with metastasis of TNBC is an urgent need. CRISPR screens have dramatically enhanced genome editing and made it possible to identify those genes associated with tumor metastasis. Methods: Here, we performed customized in vivo CRISPR screens targeting metastasis-related genes obtained from transcriptome analysis. By applying Cox proportional hazard regression models, we developed and verified a three-gene signature (RhoV, TSNARE1 and C19orf33) to predict the disease-free survival in TNBC. Next, immunoprecipitation and LC-MS/MS were conducted to explore the metastasis mechanism of RhoV. Results: The three-gene signature successfully predicts the disease-free survival in TNBC. Furthermore, our data demonstrated RhoV as a key gene involving in tumor metastasis, which was frequently upregulated in TNBC and correlated with poor survival. Knockdown of RhoV significantly suppressed cell invasion, migration and metastasis both in vitro and in vivo . In addition, we explored the physically association between RhoV and activated EGFR and verified the association was dependent on GRB2 through a specific proline-rich motif in N-terminus of RhoV. Conclusions: Taken together, our research firstly reveals that RhoV serves as an EGFR-mediated metastasis mechanism activator and thus provides a mechanistic basis for TNBC metastasis and may be a valuable therapeutic target.
Objective To produce the mouse models of vaginal microflora dysbiosis induced by antibiotic,and study the adjustment of Lactobacillus on vaginal infection.Method 50 mg/d ceftriaxone was given to the IRC mice intragastrically for 5 days and inoculated intra-vaginally with 20 μl of a suspension of Candida albicans to make mouse vaginal candidias albican imbalance model.The model mice were then inoculated intra-vaginally with 20 μl of a suspension of 2×108CFU/ml Lactobacillus.After treatment the Candida albicans and Lactobacillus were quantified by culture of vaginal lavage fluid and Papanicolaou staining of vaginal tissue.Result The amounts of Lactobacillus in the vaginal of model group decreased significantly(P0.01).White blood cells and Candida albicans were found through vaginal secretion examination by microscopy.After treatment,the amount of Lactobacillus in the vagina of the mice treated by Lactobacillus increased and recovered to normal level(P0.05),while the amount of Candida albicans decreased significantly.We also found that the rebuilt viginal microbiota could exclude Candida albicans dramatically,which indicated that the colonization resistance of the flora was recovered(P0.01).Interestingly,all of the efficiency was impressed with the Lactobacilus pre-treated group.Conclusion The adhesion of Candidias albican to vaginal mucous membrane could be prevented by Lactobacilus imported from outside the vagina.The vaginal microecosystem could be adjusted and the vaginal mucous membrane could be mended by Lactobacilus.
Abstract Background: As the commonest form of ischemic heart diseases, the Myocardial Ischemia-Reperfusion injury (MI/RI) accounts for almost 50 percent of all deaths. The prevention and treatment of MI/RI while reducing the mortality of myocardial infarction has become a raging topic of research in the cardiovascular field. At present, there are no effective drugs for the treatment of MI/RI. Hence, it becomes imperative to identify or develop efficient lead compounds for treating MI/RI. It has been reported that the Ganjiang Fuzi Decoction (GFD) could be used for the effective treatment of MI/RI due to its promotion of vasodilation and vascular endothelial cell proliferation besides reducing the oxidative damage. Methods: The network pharmacological methods were used in this study, for analyzing the biological processes and the molecular mechanisms of the GFD for MI/RI treatment. In vitro and in vivo experiments were performed for verification of the results of the network pharmacological predictions. Results: Around 16 active components of GFD were discovered against MI/RI, where aconitine, 6-ginger, mesaconitine, and hypaconitine were the leading ones with regard to the degree value. Moreover, it was found that 88 MI/RI-related targets mainly involved six aspects, apoptosis, oxidative stress, inflammation, mitochondrial energy metabolism, and vasodilation. In vitro studies indicated the ability of the GFD to increase the survival rate, decrease the apoptosis rate, reduce oxidative damage, and increase the expression of HIF-1α, VEGF, and eNOS in hypoxia/reoxygenation(H/R) injured Rat Vascular Endothelial Cells (RVEC). The in vivo studies illustrated the capacity of the GFD to reduce the myocardial tissue damage and the infarction area, while increasing the expression of HIF-1α, VEGF, and eNOS in the MI/RI rats. Conclusions: The results of this study confirmed the anti-MI/RI role of the GFD through the activation of the HIF-1α signaling pathway, promotion of vascular proliferation and dilation, and the reduction in oxidative damage. The findings of this study would further provide experimental evidence for the application of the GFD in the treatment of MI/RI.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)