Dual Immunotherapy in Advanced Non-small Cell Lung Cancer: the Progress and Clinical Application / 中国肺癌杂志

Programmed cell death protein-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors and PD-1 inhibitors plus chemotherapy combination regimens have been widely used in the first-line treatment of advanced non-small cell lung cancer(NSCLC), but patients with low PD-L1 expression have limited objective response and survival benefits. Existing treatment regimens are still difficult to fully meet the clinical needs of patients in the real world. Therefore, researchers are still exploring novel superactive treatment options to further improve the efficacy and survival prognosis of different sub-groups in NSCLC. Dual immunotherapy [such as the combination of PD-1 and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitors] has shown considerable long-term survival benefits in a variety of tumors and has also shown broad clinical prospects in NSCLC. In addition to exploring different emerging combination options, how to accurately identify the optimal-benefit groups through predictive biomarkers and how to effectively manage the safety of combination immunotherapy through multidisciplinary collaboration are also the focus of dual immunotherapy. This article reviews the mechanism of action, research progress, predictive biomarkers and future exploration directions of dual immunotherapy.
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Detection of Rare Mutations in EGFR-ARMS-PCR-Negative Lung Adenocarcinoma by Sanger Sequencing

PURPOSE: This study aimed to identify potential epidermal growth factor receptor (EGFR) gene mutations in non-small cell lung cancer that went undetected by amplification refractory mutation system-Scorpion real-time PCR (ARMS-PCR). MATERIALS AND METHODS: A total of 200 specimens were obtained from the First Affiliated Hospital of Guangzhou Medical University from August 2014 to August 2015. In total, 100 ARMS-negative and 100 ARMS-positive specimens were evaluated for EGFR gene mutations by Sanger sequencing. The methodology and sensitivity of each method and the outcomes of EGFR-tyrosine kinase inhibitor (TKI) therapy were analyzed. RESULTS: Among the 100 ARMS-PCR-positive samples, 90 were positive by Sanger sequencing, while 10 cases were considered negative, because the mutation abundance was less than 10%. Among the 100 negative cases, three were positive for a rare EGFR mutation by Sanger sequencing. In the curative effect analysis of EGFR-TKIs, the progression-free survival (PFS) analysis based on ARMS and Sanger sequencing results showed no difference. However, the PFS of patients with a high abundance of EGFR mutation was 12.4 months [95% confidence interval (CI), 11.6−12.4 months], which was significantly higher than that of patients with a low abundance of mutations detected by Sanger sequencing (95% CI, 10.7−11.3 months) (p < 0.001). CONCLUSION: The ARMS method demonstrated higher sensitivity than Sanger sequencing, but was prone to missing mutations due to primer design. Sanger sequencing was able to detect rare EGFR mutations and deemed applicable for confirming EGFR status. A clinical trial evaluating the efficacy of EGFR-TKIs in patients with rare EGFR mutations is needed.

The antioxidant effect of serum bilirubin in lung cancer / 实用医学杂志

Objective To study the antioxidant effect of serum bilirubin,an endogenous antioxidants,in the patients with lung cancer. Methods A total of 402 patients with lung cancer(patient group)and 422 healthy individuals(control group)were enrolled in this study. The concentrations of total bilirubin(TBIL)and direct bili-rubin(DBIL)were measured using Diazonium Salts reagent on an automated chemistry analyzer(AU5821,Beck-man Coulter)and concentrations of indirect bilirubin(IBIL)were calculated based on concentrations of TBIL and DBIL. The total activity of SOD and MDA concentrations of 104 patients and 57 controls were measured using Xan-thine oxidase and TBA reagents respectively. All data were analyzed using SPSS 19.0 Software. Results Compared with the control group,the concentrations of TBIL,DBIL,IBIL and the activity of SOD in the patient group were decreased(P < 0.05)but the concentrations of MDA were increased. However,no tendency was found from T1 to T4(TNM)groups. Conclusion There is antioxidant dysfunction within patient with lung cancer and the serum bilirubin would be involved in this process.

Clinical analysis of 36 cases of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4 / 中华肿瘤杂志

Objective@#To analyze the treatment of advanced non-small cell lung cancer (NSCLC) with performance status (PS) scores between 2 and 4, in order to improve the diagnosis and treatment of these patients.@*Methods@#A total of 36 patients with advanced NSCLC with hypoxemia were reviewed. The clinical data of disease characteristics, etiology, complications, manifestation, therapy, progression, and secondary biopsy were collected. The clinical efficacy was graded according to the Response Evaluation Criteria In Solid Tumors (RECIST): complete response (CR), partial response (PR), stable disease (SD) and disease progression (PD).@*Results@#All patients had hypoxemia, of whom 86.1% (31 patients) had complications and 55.6% (20 patients) had noninvasive ventilator for respiratory support. 77.8% (28 cases) received broad-spectrum antibiotic treatment, and 78.6% of them got lung osmotic relief after the anti-infection treatment. 15 cases received bedside fiberoptic bronchoscopy suction, of whom two cases were treated with airway stent deposition due to airway obstruction, four cases with thoracic drainage, four cases with anticoagulation, and one with thrombolytic therapy. After these supportive treatment, the PS score of these patients decreased from 3.4±0.5 to 2.5±0.7, while SPO2 improved from (89.0±5.2)% to (95.0±3.5)%. As first-ling anti-cancer treatment, nine patients were administrated with targeted medicine orally, 13 patients with a combined chemotherapy of pemetrexed plus bevacizumab or carboplatin, eight patients with paclitaxel plus carboplatin, four patients with gemcitabine plus carboplatin, and two patients with docetaxel plus gemcitabine. In the first response evaluation, there were one case of CR, 23 cases of PR, four cases of SD, and eight cases of PD, with a clinical benefit rate of 66.7% and a disease control rate of 77.8%. A total of 22 patients experienced disease progression, of whom eight cases had a secondary biopsy and six cases had gene sequencing. Of these 36 patients, 10 (27.8%) patients survived at the last follow-up, with a progression-free survival of (10.0±6.5) months.@*Conclusion@#Besides prompt anti-cancer treatment and best supportive treatment should be incorporated to improve PS and improve outcome.

Effects of Compound Kushen Tang on Ulcerative Colitis in Rats and the Underlying Mechanism / 中国药师

Objective: To investigate the therapeutic effects of compound Kushen Tang and its relevant mechanism in TNBS-in-duced ulcerative colitis ( UC) rats. Methods:UC was induced by TNBS in rats. After compound Kushen Tang was given orally, the levels of MDA, iNOS, and NO and the activity of MPO, SOD, and GSH-Px were measured. The general condition of rats and colon tissue morphology were observed. Results:The levels of MDA (P<0. 05), iNOS (P<0. 01) and NO (P<0. 01) and the activity of MPO (P<0. 01) in tissues of UC rats were significantly higher than the control group. The activity of SOD (P<0. 01) and GSH-Px (P<0. 05) were significantly lower than those in the control group. After the treatment with high doses of compound Kushen Tang, the levels of MPO (P<0. 01), MDA (P<0. 05), iNOS (P<0. 05) and NO (P<0. 01) were significantly decreased, and the activity of SOD (P<0. 01) and GSH-Px (P<0. 05) significantly increased. The therapeutic effect was dose-dependent and the general con-dition of rats and colon tissue morphology were also significantly improved. Conclusion:Compound Kushen Tang is considered as a no-vel therapeutic alternatives for the treatment of UC, which can reduce coloni inflammatory injury and ameliorate the colitis.

Clinical efficacy of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinical efficacy and toxicity of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy.</p><p><b>METHODS</b>Two hundred and eighty-three patients with stage 3/4 lung adenocarcinoma treated at our hospital from August 2010 to August 2013 were included in this study. The lung adenocarcinomas in all the 283 patients were confirmed by pathology or cytology, all were EGFR-negative, and all patients received pemetrexed second line chemotherapy. The 283 patients were randomly divided into two groups: the improved treatment group (142 cases) and the conventional treatment group (141 cases). The patients of conventional treatment group received 400 µg folic acid per os daily for 7 days before the first dose of pemetrexed, and continued until 21 days after the last dose of pemetrexed. Besides, they received 1000 µg vitamin B12 injection at 7 days before the first dose of pemetrexed, and once per cycle of pemetrexed for 3 cycles after the last dose of pemetrexed. The patients of the improved treatment group took 400 µg folic acid daily per os from the day before the first dose to 21 days after the last dose of pemetrexed. They also received 500 µg vitamin B12 by injection one day before the first dose, and one day before each therapy cycle of pemetrexed therapy.</p><p><b>RESULTS</b>The mean number of cycles of pemetrexed chemotherapy was 4 in both groups. In the 142 patients of improved treatment group, complete response (CR) was observed in two cases, partial remission (PR) in 28, stable disease (SD) in 21, and progressive disease (PD) in 91 cases, with a total effective rate of 21.1%. While in the conventional treatment group, CR was observed in one case, PR in 27 cases, SD in 23 cases, and PD in 90 cases, with a total effective rate of 19.9%. The median progression-free survival (PFS) was 3.8 months in the improved treatment group and 4.2 months in the conventional treatment group (P=0.143). The toxicity of chemotherapy was mild in both groups, with no significant difference between the two groups (P>0.05). The most common side effects of hematological system were leukopenia and neutropenia, and the most common side effects of non-blood system were nausea and vomiting. The most common grade 3-4 toxic reaction in both groups was leukopenia and neutropenia, with no significant difference between the two groups (P>0.05). Multivariate analysis showed that the age of patients was an independent factor of grade 3-4 chemotherapy toxic reaction (P<0.05), while gender, the baseline level of PS score or blood system had no significant effect on the grade 3-4 chemotherapy toxic reaction (P>0.05).</p><p><b>CONCLUSIONS</b>Compared with the conventional treatment scheme, the improved treatment scheme has similar therapeutic effects and could be used more conveniently, while the toxic effects of chemotherapy are not increased at the same time. Our results indicate that pemetrexed-based chemotherapy does not need to delay the chemotherapy because of vitamin support treatment.</p>

Effect of Ghrelin on L-type Calcium Channel Current of Ventricular Myocytes in Experimental Rats / 中国循环杂志

Objective: To study the effect of ghrelin on L-type calcium channel current (ICa-L) of ventricular myocytes in experimental rats. Methods: The single ventricular myocyte in experimental rats were obtained by enzymolysis method, and the whole-cell patch-clamp technique was used to investigate the effect of ghrelin on ICa-L of ventricular myocytes at different doses of 10 nmol/L, 100 nmol/L and 1μmol/L respectively. Results: Ghrelin at 10 nmol/L, 100 nmol/L and 1μmol/L may inhibit ICa-L at (8.95 ± 2.13) %, (31.18 ± 4.78) % and (64.63 ± 8.57)% respectively,P<0.05, and the current-voltage curve was shifted upwards. The channel half inactivation curve decreased from (-1.34 ± 1.9) mV to (-8.04 ± 1.32 ) mV, (9.76 ± 1.17) mV and (-11.81 ± 0.73) mV respectively,P<0.05, and the recovery time after inactivation was prolonged as τ value from (63.23 ± 9.32) to (98.95 ± 10.74), (109.56 ± 13.42) and (127.39 ± 16.13) respectively,P<0.05. Conclusion: Ghrelin may accelerate ICa-L inactivation and prolong the recovery time after inactivation. Ghrelin inhibits ICa-L in a dose-dependent manner.

Protection Effect of Wogonin on Mice with Hyperlipidemia / 医药导报

Objective To explore the effects of wogonin on hyperlipidemia in mice and clarify the molecule mechanism. Methods Thirty mice were evenly divided into three group normal control group,model control group and treatment group. The normal control group was given normal diet,the model control group received high-fat diet,the treatment group received high-fat diet with wogonin (500 mg·kg-1 ). Results The mice developed hyperlipidemia 12 weeks after starting the high-fat diet. The body weight,visceral fat and fat index were increased (P<0. 05). After treatment,these indices were reduced ( P < 0. 01). Wogonin significantly reduced the total cholesterol ( TC),low density lipoprotein ( LDL),high density lipoprotein (HDL),except the triglyceride (TG). Compared to the model control group,the hepatic lipase(HL) and lipoprotein lipase(LPL) activity in the treatment group were recovered (P<0. 05),but HMG-CoA reductase activity was inhibited ( P<0. 01). Mechanistic study suggested that the lipid-lowering effect might be related to the lipid synthesis genes (SREBP-1c,FAS, PPARγ) and the lipid metabolism genes (PPARα,CPT-1). Conclusion Wogonin can prevent hyperlipidemia,which might be related to the regulation of enzyme activity and the changes of lipid synthesis and oxidative metabolism.