Research Progress on Combination of Radiotherapy and Immunotherapy on Advanced Non-small Cell Lung Cancer with Negative Driver Genes / 肿瘤防治研究

A large proportion of patients with non-small cell lung cancer (NSCLC) are diagnosed with metastatic and incurable advanced lung cancer at the time of discovery, so these patients are given no surgical opportunity and have a low 5-year survival rate. In the era of immunotherapy, many kinds of immune checkpoint inhibitors (ICIs) have been approved as the first/second-line treatment for patients with advanced NSCLC with negative driving genes and have been combined with radiotherapy as an important treatment strategy for patients with advanced NSCLC. The innovative strategy of combining radiotherapy and immunotherapy has shown feasibility as supported by practical evidence in clinical research. A preclinical experiment of observing the immune mechanism at the molecular and cellular levels preliminarily revealed the interaction among tumor, radiation, and immune system. This paper briefly reviews the progress of combined radiotherapy and immunotherapy in the treatment of advanced NSCLC with negative drvier genes.

Inhibitory Effect and Target Prediction of Genistein on the Growth of Human Nasopharyngeal Carcinoma CNE 1 Cells / 中国药房

OBJECTIVE：To study the inhibi tory effects of genistein on the growth of human nasopharyngeal carcinoma. CNE 1 cells and predict its potential target. METHODS ：CCK-8 method was used to test the effects of 0（blank control ），12.5，25，50， 100，150 µmol/L genistein on the proliferation of CNE 1 cells after treated for 24，48，72 h. Flow cytometry was carried out to detect the effects of 0（blank control ），15，30，60 µmol/L genistein on the cell cycle and ap optosis of CNE 1 cells after treated for 24 h. Scratch test was used to investigate the effects of 0（blank control ）， 10， 20， 30 µmol/L genistein on themigration ability of CNE 1 cells after treated for 24 h. High （No.18210156） throughput sequencing was conducted to discover the differential genes in CNE 1 cells after treated with 0（blankcontrol），30 µmol/L genistein for 24 h. RT-qPCR assay was adopted to verify the mRNA expression of related differential genes in above trials. RESULTS ： Compared with blank control，12.5，25，50，100，150 µmol/L genistein sho wed significant inhibitory effect on the proliferation of CNE 1 cells（P＜ 0.01），in a concentration- time-effect manner ；15，30 µmol/L genistein could arrest CNE 1 cell cycle at G 0/G1 stage（P＜0.05 or P＜ 0.01）；30，60 µmol/L could arrest CNE 1 cell cycle at G 2/M stage and promoted cell apoptosis （P＜0.05 or P＜0.01）. 10，20，30 µmol/L genistein could significantly inhibit the migration ability of CNE 1 cells（padj＜0.01）. High throughput sequencing revealed a total of 2 271 differentialgenes（P＜0.05），1 154 of which were up-regulated while 1 117 of which were down-regulated ；8 potential target genes ，including p53，p21，STC2，FGF2，CDK6，CYCLIN D ，PI3K，AKT，were screened by cell experiment. After validated by RT-qPCR assay ，mRNA expression of p53，p21，STC2，FGF2，CDK6，CYCLIN D and AKT were significantly down-regulated（P＜0.05），which consistent with the sequencing results. CONCLUSIONS ：Genistein can effectively inhibit the growth of human nasopharyngeal carcinoma CNE 1 cells，the mechanism of which may associated with inhibiting the expression of mutant gene p53，restoring the function of wild-type P 53 protein and inhibiting the activity of PI 3K/Akt pathway.

Effect of Polyphenols fromRubus suavissirnuS. Lee on Spontaneous Hypertensive Rats / 世界科学技术-中医药现代化

This article was aimed to study the effect of polyphenols fromRubus suavissirnusS. Lee (RSLP) on spontaneous hypertensive rats (SHR) and to explore its mechanism of anti-hypertensive. The water extraction of RSLP was prepared. And the polyphenols was extracted with macroporous resin. The non-invasive blood pressure analysis system was used to detect the blood pressure. SHR model was selected to study the anti-hypertensive effect. The 16 normal Wistar rats were randomly divided into the control group and the normal RSLP high-dose group (RSLP-NH). The 40 SHR were randomly divided into the model group, Captopril group, RSLP-L group, RSLP-M group and RSLP-H group. SBP, DBP, HR, body weight and organ index were observed after the drug administration for 8 weeks and drug withdrawal for 2 weeks. The contents of SOD, MDA, GSH-Px, NO, NOS and ANP in serum were measured. The results showed that the blood pressure of SHR was significantly higher than that of the control group, which can be used for anti-hypertensive studies. Each RSLP group can obviously reduce the SBP and DBP of SHR (P 0.05). RSLP can elevate GSH-Px, SOD levels and reduce the activity of MDA (P < 0.05). RSLP can reduce NO, NOS and ANP contents in serum (P < 0.05). It was concluded that RSLP can significantly reduce the SBP and DBP of SHR, but it had no significant effect on HR. It can increase the activity of GSH-Px, SOD, NO, NOS levels, and reduce the contents of MDA, ANP in serum. It had certain inhibitory effect on the left ventricular hypertrophy.

Study on Anti-inflammatory Effects and Mechanism of Petroleum Ether Extract from Citrullus lanatus Vine / 世界科学技术-中医药现代化

This article was aimed to study anti-inflammatory effects of petroleum ether extract from Citrullus lanatus vine (PEECLV) and explore the mechanism. The methods of ear swelling with xylene, increasing of peritoneal capil-lary permeability, and paw edema with egg albumin were used in the establishment of mice models, respectively. Granuloma with cotton pellet, and paw edema with carrageenan were used in the establishment of rat models, re-spectively. Observation was made on anti-inflammatory effects of PEECLV. The content of nitrous oxide (NO) and nitric oxide synthase (NOS), as well as the level of TNF-α and IL-1β in blood serum were measured among granu-loma with cotton pellet rat models. Contents of malondialdehyde (MDA), prostaglandin E2 (PGE2), 5-HT, histamine (His), and protein in inflammatory exudates from the paw edema with carrageenan rat model, as well as contents of NO and NOS in blood serum, and activity of superoxide dismutase (SOD) were measured in order to study the possi-ble anti-inflammatory effects. The results showed that PEECLV can suppress the ear swelling with xylene, the in-creasing of peritoneal capillary permeability, and the paw edema with egg albumin in mice, as well as granuloma with cotton pellet, paw edema with carrageenan in rats. It had anti-inflammatory effects at different degrees. The content of NO and NOS, as well as the level of TNF-α and IL-1β in blood serum were reduced in granuloma with cotton pellet rat models. The content of MDA, PGE2, 5-HT, His, and protein content were reduced in inflammatory exudates from the paw edema with carrageenan rat model. The increasing of NO and NOS in blood serum was inhib-ited. And the activity of SOD was increased. It was concluded that PEECLV had certain anti-inflammatory effects. Its mechanism may be related to the influence of the production of inflammatory mediators and antioxidant.

Radiation sensitization by dihydroartemisinin on human HeLa cells of cervical cancer / 中华放射医学与防护杂志

Objective To investigate the radiosensitizing effects of dihydroartemisinin(DHA)on human HeLa cells of cervical cancer irradiated by X rays.Methods Cell growth kinetics was determined using MTF assay.Cell survival was analyzed by elonogenic assay.The change of cell cycle and apeptosis was measured by flow cytometry.Results Dihydroartemisinin inhibited the growth of HeLa cells of human cervical cancer and showed a dose-dependent and time-dependent manner.Dihydroartemisinin(20 μmol/L)showed the radiosensitizing effects on HeLa cells,and the sensitizing enhancement ratio(SER)was 1.47.Dihydroartemisinin abrogated radiation-induced G2 arrest of the tested HeLa cells,the G2 ratio of medicine + radiation group dechned from 73.58% to 48.31%.Dihydroartemisinin enhanced the apoptosis of HeLa cells by X-irradiation,the apoptosis rates of medicine + radiation group significantly increased from 29.46%,48.04%,70.21% to 45.79%,66.36% and 79.58%,respectively for 2,4 and 6 Gy.Conclusions Dihydroartemisinin could increase the radiesensitivity of HeLa cells of human cervical cancer.Abrogation of radiation-induced C2 arrest could be part of the mechanism.

Radiation sensitization by CAPE on human HeLa cells of cervical cancer / 中华放射医学与防护杂志

Objective To study the radiosensitizing effect of caffic acid phenethyl ester(CAPE)on human cervical cancer HeLa cells.Methods MTT assay was used to measure the relation between the inhibition effect and CAPE concentrations by CAPE with different concentrations on HeLa cells for 24 hours.HeLa cells were divided into the control and experimental groups,both of which were given 0,2,4,6 and 8 Gy of 60Co γ-irradiation,respectively.The cell clones were counted.Meanwhile HeLa cells were divided into the control,CAPE,irradiation and combination groups.Flow cytometric analysis was adopted to detect the changes of cell cycle distribution induced by CAPE.Results The inhibition rate of CAPE acting on Hela cells increased with concentrations(F=126.49～3654.88,P＜0.01).HeLa cells cloning survival decreased with the increase of radiation dose(F=174.42～9422.81,P＜0.01).At the game radiation dose,HeLa cells cloning survival was less in experimental group than conlrol group(F=120.14～251.91,P＜0.01).The mean lethal dose(D0)(1.45 and 1.82 Gy)and the quasi-threshold dose(Dq)(1.89 and 3.21 Gy)of HeLa cells in experimental group decreased comparing with control group,SER was 1.26.Compared with the sole irradiation group,cells in G2/M phase of the CAPE group and the sole irradiation group increased(P＜0.01)while the combination group decreased(P＜0.01).Conclusions CAPE could increase the radiation sensitivity of HeLa cells by G2/M arrest and may be related to the inhibition of the sub-lethal damage repair.