1.Mechanisms of tumor cell’ s apoptosis triggered by gold nanorods
Fulei ZHANG ; Cheng JIANG ; Changhong KE ; Tai YU ; Sufen LI ; Shangjing GUO ; Wei LI
Chinese Journal of Biochemical Pharmaceutics 2015;37(4):42-44,47
Objective To explore the mechanism that gold nanorods trigger apoptosis in cancer cells.Methods Gold nanorods was synthesized by gold seed growing method, and its characterization was detected; gold nanorods on cell proliferation-toxicity were evaluated by CCK-8 Kit and apoptosis were detected by flow; mitochondrial membrane potential were tested by JC-1 and activation of Caspase 9 and Caspase 3 were detected by western blot. Results The results found that gold nanorods had nontoxic to normal cells, but highly toxic to tumor cells; and with the increasing of gold nanorods’ working time, the percentage of apoptotic cancer cells was increasing; in addition to, normal cells’ mitochondrial membrane potential did not change, but cancer cells had a significant reduction in mitochondrial membrane potential.Conclusion This study proves that gold nanorods induce apoptosis through the mitochondrial apoptosis pathway.
2.Efficacy and Safety of KRASG12C Inhibitors in Advanced Solid Tumors with KRASG12C-mutated: A Single-arm Meta-analysis
Dengxu TAN ; Ke LIU ; Yifan MA ; Yongfeng WANG ; Yanying ZHANG ; Changhong SHI
Cancer Research on Prevention and Treatment 2023;50(7):688-693
Objective To systematically study the efficacy and safety of KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated. Methods Computer searches from PubMed, The Cochrane Library, Web of Science, Embase, CNKI, and CBM databases were conducted to collect clinical studies on KRASG12C inhibitors in advanced solid tumors with KRASG12C-mutated, with a search time from inception to October 12, 2022. Then, two investigators independently screened the literature, extracted information, assessed the risk of bias in included studies, and performed meta-analyses using RevMan 5.4 software. Results There were four publications included, all of which were single-arm clinical studies. The KRASG12C inhibitors that completed clinical phase Ⅰ and Ⅱ trials were sotorasib and adagrasib, with two publications each. A total of 388 and 394 patients were included in the efficacy evaluation and safety evaluation, respectively. Resultsof the Meta-analysis showed that the patients had objective response rate, overall disease control, and disease stabilization rates of 35%, 82%, and 45%, respectively. In addition, the rate of serious adverse events, general adverse events, and all adverse events in patients was 2%, 28%, and 79%, respectively. Moreover, the rate of partial remission of disease in NSCLC patients was 38%. Conclusion The KRASG12C inhibitors sotorasib and adagrasib exhibited good efficacy and high safety in advanced solid tumors.
3.Correlation of radiomic features based on diffusion weighted imaging and dynamic contrast-enhancement MRI with molecular subtypes of breast cancer
Peiqi WU ; Ke ZHAO ; Lei WU ; Zaiyi LIU ; Changhong LIANG
Chinese Journal of Radiology 2018;52(5):338-343
Objective To explore the relationship between radiomics signatures based on DWI and dynamic contrast-enhanced MRI (DCE-MRI) and molecular subtypes of breast cancer.Methods A retrospective analysis of 79 female breast cancer patients, with single mass, clear molecular subtypes and preoperative breast MRI scanning (obtaining DCE-MRI and ADC images), of Guangdong General Hospital from June 2015 to June 2016,were performed.Traditional quantitative parameters,including ADC value and initial enhancement rate(IER),were recorded.Texture analysis were performed on ADC map and DCE map, with manual segmentation and extraction of radiomic features,and Manual segmentation was performed on ADC map and DCE map, radiomics features were extracted and 10 radiomics signatures were finally selected after dimension reduction. Four molecular subtypes of breast cancer were classified by immunohistochemical detection of pathological specimens, including Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER2) overexpression and triple negative (TN). Univariate logistic regression analysis was used for assessing the performance of ADC values, IER values and radiomics signatures to independently predict molecular subtypes groups.Multivariate logistic regression analysis was performed to establish predicting models, then receiver operating characteristic curves (ROC) were drawn and areas under ROC curve were calculated to compare the diagnostic performance of each model. The Hosmer-Lemeshow test was performed to test the goodness of model fitness. Results There were 29 cases of Luminal A, 39 cases of Luminal B, 5 cases of HER2 overexpression and 6 cases of TN breast cancer patients.Univariate logistic regression analysis was used to assess the ability of traditonal MRI parameters of ADC and IER values and ten of the radiomics siganitures in classifying molecular subtypes,results showed that the AUC values of ADC and IER values, were both less than 0.70 (range 0.516 to 0.605), which indicated valueless;at least one radiomic signature had AUC greater than 0.70 when identifying each molecular subtype, and AUC of DCE_L_G_2.5_autocorrelation achieved the highest value of 0.941 in identifying TN and non-TN subtypes.Multivariate logistic regression analysis were performed to obtain the best model, results showed that the AUCs for classifying Luminal A and non-Luminal A, Luminal B and non-Luminal B, TN and non-TN subtypes were 0.786 and 0.733 And 0.941, respectively. The Hosmer-Lemeshow test showed that the P values of all models were larger than 0.10 (0.156, 0.204 and 0.820,respectively),indicating that there was no significant difference between the predicted and observed values of each model established, these models were all fitted good. Conclusion The radiomics features based on ADC map and DCE map can help to identify the molecular subtypes of breast cancer,especially for the identification of TN type breast cancer.
4.Repairing Effects of Ginsenoside Rg1 on Traumatic Brain Injury in Mice
Wenwen GUO ; Ya ZHAO ; Yinghua WANG ; Ke LIU ; Xu GE ; Yanying ZHANG ; Yongfeng WANG ; Changhong SHI
Laboratory Animal and Comparative Medicine 2023;43(3):243-252
Objective To explore the effects of ginsenoside Rg1 on blood-brain barrier, neuroinflammation and behavioral function of traumatic brain injury (TBI) mouse model.MethodsThe experiment was divided into two parts. In the first part, 27 SPF male BALB/c mice were randomly divided into blank group, sham operation group and TBI model group, with 9 mice in each group. TBI model group was made by controlled cortical impact (CCI) after craniotomy, while sham operation group was only performed craniotomy without any treatment, and the blank group was not treated at all. The effect of modeling was evaluated after operation. In the second part, 50 male BALB/c mice were randomly divided into sham operation group, three different drug dosage groups and solvent (DMSO) control group, with 8 mice in each group. The drug treatment groups were injected with ginsenoside Rg1 at the doses of 10, 20 and 40 mg/kg respectively 6 hours after TBI model had been successfully established, while the DMSO control group was given the same amount of 1% DMSO for one week, twice a day. Modified neurological severity scores (mNSS) were performed on the 1st, 3rd, 7th and 14th day after modeling, and the blood-brain barrier leakage was detected by Western blotting on the 3rd day after modeling. On the 14th and 16th day, the elevated cross maze test and water maze test were used to detect the neurobehavioral function. On the 28th day after anesthesia and perfusion, the brains were taken out, and the neuroinflammation such as activation of microglia and astrocytes was observed by immunofluorescence staining.ResultsThe expression level of MMP-9, a marker of blood-brain barrier, decreased in ginsenoside Rg1 treatment group (P<0.01). The number of microglia (Iba-1 positive) and astrocyte (GFAP positive) cells decreased significantly (P<0.05), which indicated that neuroinflammation was inhibited, and the best effect was achieved at the dosage of 20 mg/kg (P<0.01). The mNSS of mice in ginsenoside Rg1 treatment group were significantly lower than those in DMSO control group (P < 0.01), and the proportion of times they entered the open arm was significantly higher than that in DMSO control group (P < 0.05). The time ratio in the quadrant where the water maze experimental platform was located and the times of crossing the platform were significantly higher than those in control group (P < 0.05), and the dosage of 20 mg/kg had the best effect.ConclusionThe TBI mouse model was successfully constructed and applied to the study of ginsenoside Rg1 repair of mouse traumatic brain injury. Ginsenoside Rg1 can significantly improve blood-brain barrier, alleviate neuroinflammation and improve neurobehavioral function in TBI model mice, and the effect is the most significant at the dose of 20 mg/kg.