ABSTRACT
Objective: To construct and validate a nomogram model integrating the magnetic resonance imaging (MRI) radiomic features and the kinetic curve pattern for detecting metastatic axillary lymph node (ALN) in invasive breast cancer preoperatively. Materials and Methods: A total of 145 ALNs from two institutions were classified into negative and positive groups according to the pathologic or surgical results. One hundred one ALNs from institution I were taken as the training cohort, and the other 44 ALNs from institution II were taken as the external validation cohort. The kinetic curve was computed using dynamic contrast-enhanced MRI software. The preprocessed images were used for radiomic feature extraction. The LASSO regression was applied to identify optimal radiomic features and construct the Radscore. A nomogram model was constructed combining the Radscore and the kinetic curve pattern. The discriminative performance was evaluated by receiver operating characteristic analysis and calibration curve. Results: Five optimal features were ultimately selected and contributed to the Radscore construction. The kinetic curve pattern was significantly different between negative and positive lymph nodes. The nomogram model showed a better performance in both training cohort [area under the curve (AUC) = 0.91, 95% CI = 0.83-0.96] and external validation cohort (AUC = 0.86, 95% CI = 0.72-0.94); the calibration curve indicated a better accuracy of the nomogram model for detecting metastatic ALN than either Radscore or kinetic curve pattern alone. Conclusion: A nomogram model integrated the Radscore and the kinetic curve pattern could serve as a biomarker for detecting metastatic ALN in patients with invasive breast cancer.
ABSTRACT
OBJECTIVE: To apply mixed logit model for analyzing the data of new rural cooperative medical with suitability and identify the factors affecting the residents choices of insurance mode. METHODS: Hypothesis test of IIA was performed using the mogtest module of Stata10.0 to test the eligibility of the condition. The mixed logit model was established to allow the parameters to vary in the population using SAS9.1 MDC module. RESULTS: The data in this study did not satisfy the IIA assumption (P<0.01), so that the multinomial logit model was not applicable. The adjusted Estrella of the mixed logit model was 0.6658. CONCLUSION: The mixed logit approach does not rely on the restrictive IIA assumption and allows for correlation patterns between choices and individual variation. This approach can help in the determination of the choices in new rural cooperative medical system.
Subject(s)
Health Care Coalitions/statistics & numerical data , Rural Health Services/statistics & numerical data , Insurance, Health , Logistic Models , Rural HealthABSTRACT
PI-103, the first synthetic multitargeted compound which simultaneously inhibits PI3Kalpha and mammalian target of rapamycin (mTOR) shows high antitumor activity in glioma xenografts. In the present study, clear antitumor activity was observed with PI-103 treatment in two gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines, A549 and H460, by simultaneously inhibiting p70s6k phosporylation and Akt phosphorylation in response to mTOR inhibition. In addition, H460 cells with activating mutations of PIK3CA were more sensitive to PI-103 than A549 cells with wild-type PIK3CA. PI-103 was found to inhibit growth by causing G0-G1 arrest in A549 and H460 cells. Western blotting showed that PI-103 induced down-regulation of cyclin D1 and E1 and simultaneously up-regulated p21 and p27, associated with arrest in the G0-G1 phase of the cell cycle. Furthermore, p53, the tumor suppressor which transcriptionally regulates p21, was also upregulated with PI-103 treatment. Collectively, our results suggest that multitargeted intervention is the most effective tumor therapy, and the cooperative blockade of PI3Kalpha and mTOR with PI-103 shows promise for treating gefitinib-resistant NSCLC.
Subject(s)
Antineoplastic Agents/pharmacology , Furans/pharmacology , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/pharmacology , Protein Kinases/metabolism , Pyridines/pharmacology , Pyrimidines/pharmacology , Carcinoma, Non-Small-Cell Lung , Cell Cycle/drug effects , Cell Cycle Proteins/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Class I Phosphatidylinositol 3-Kinases , Drug Resistance, Neoplasm , Gefitinib , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms , Mutation , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Quinazolines/pharmacology , TOR Serine-Threonine Kinases , Tumor Suppressor Proteins/metabolismABSTRACT
Potassium channel dysfunction has been implicated in apoptosis in many pathological conditions. However, which Kv channel subunit is involved in glutamate-induced apoptosis remains unknown. In this study, the contributions of nine Kv alpha and three Kv beta subunits to glutamate-induced hippocampal neuronal apoptosis were investigated. Results showed that neuronal apoptosis was not obvious with 12 hr incubation of glutamate but increased markedly after 18 hr, which was attenuated by the Kv channel blocker TEA. Among all the Kv subunits investigated, gene and protein expression of Kv2.1 increased significantly before the appearance of neuronal apoptosis, whereas the Kv1.1 mRNA level decreased quickly, and protein expression was reduced gradually after the insult. Seven other Kv alpha subunits and three Kv beta subunits were not obviously affected over time. In addition, Kv1.1 overexpression could reduce glutamate-induced hippocampal neuronal apoptosis. Therefore, the alterations of Kv1.1 and Kv2.1 might contribute to glutamate-induced toxicity in hippocampal neurons. These findings suggest that these two Kv channel subunits may represent potential therapeutic targets for neuropathological conditions in which glutamate-induced toxicity is thought to contribute to neuronal dysfunction.
Subject(s)
Apoptosis/physiology , Glutamic Acid/metabolism , Kv1.1 Potassium Channel/metabolism , Neurons/metabolism , Shab Potassium Channels/metabolism , Animals , Blotting, Western , Cells, Cultured , DNA Fragmentation , Hippocampus/drug effects , Hippocampus/metabolism , In Situ Nick-End Labeling , Neurons/drug effects , Neurons/pathology , Potassium Channel Blockers/pharmacology , Potassium Channels, Voltage-Gated/metabolism , Rats , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
OBJECTIVE: To analyze the incidence trends of primary liver cancer (PLC) in Qidong. METHODS: Data of PLC incidence from 1975 to 1999 in Qidong were analyzed to delineate temporal trends and birth cohort patterns, using age-period-cohort models. RESULTS: Significant moderation or decreasing trends were began to notice in incidence rates on cohorts born in 1913 - 1917 and 1958 - 1962. CONCLUSION: Results showed that the incidence risk of the birth cohorts after 1958 - 1962 started to decline. The changes were possibly associated with the implementation of some practical measures on prevention.
