Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced non-small cell lung cancer： a meta-analysis

Objective： To evaluate the clinical efficacy of Shenqi Fuzheng injection combined with gemcitabine plus cisplatin（GP） in the treatment of advanced non-small cell lung cancer （NSCLC）. Methods： we performed a systematicsearch in the electronic databases such as Cochrane Library, Pubmed, Embase, Chinese Journal Full-text Database,Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Full-text Database andWanfang Database up to 30 January 2017. Randomized controlled trials （RCT） of Shenqi Fuzheng Injectioncombined with GP chemotherapy in the treatment of advanced NSCLC were searched, and all the RCTs wereconducted on methodological quality assessment. Data extraction and data analysis were according to standards ofCochrane systematic review. Results： Eight trials were included including a total of 701 patients. Meta-analysisresults： Shenqi Fuzheng injection combined with GP chemotherapy could significantly improve the functionalstatus of patients with NSCLC （OR = 3.44, 95% CI [2.26, 5.25], P 〈 0.0001） and clinical treatment efficacy （OR =（OR = 0.31, 95%CI [0.20, 0.47], P 〈 0.0001. The rate of leukopenia （OR = .31, 95%CI [0.20,0.47], P 〈 0.0001）,thrombocytopenia （OR = 0.58, 95%CI [0.37, 0.91], P = 0.020）, hemoglobin decline （（OR = 0.31, 95%CI [0.16,0.59], P = 0.0004） and incidence of gastrointestinal reactions （OR = 0.58,P 〈 0.05） could be reduced. Conclusion：Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced NSCLC obtainedsignificantly clinical efficacy. The quality of the literature incorporated is low, the conclusion requires high-qualityresearch to further prove.

^(18)F-FETNIM PET/CT hypoxia imaging in non-small cell lung cancer:preliminary clinical observation

Objective:The aims of this study were to evaluate potential side effects of 18F-fluoroerythronitroimidazole (18F-FETNIM) as a new-type hypoxia-imaging agent and to investigate the feasibility of 18F-FETNIM PET imaging in advanced non-small cell lung cancer (NSCLC) patients and the correlations of hypoxia extent with tumor volume or pathological type. Methods: Twenty-six NSCLC patients were prospectively included in the study. PET/CT scans were performed 2 h after intravenous injection of 18F-FETNIM in all 26 patients. A pixel-by-pixel calculation of tumor to blood (T/B) activity ratio for all image planes was calculated. The number of pixels in the tumor volume with a T/B ratio≥ 1.5,indicating significant hypoxia,was determined and converted to mL units to measure the hypoxia volume (HV). Results: The images were clearly identified after 2 h post-injection of 18F-FETNIM. The tumors in 4 cases were not distinguished from background,while the remaining 22 displayed local 18F-FETNIM uptake in thoracic lesions moderately to markedly higher than background. There was no correlation between 18F-FETNIM uptake with pathological type. There were significant correlations of HV and also the T/B ratio with tumor volume. Conclusion:18F-FETNIM is a promising hypoxia-imaging agent which clinical use is safe and satisfactory. The preliminary study provides valuable methods and experience to its further research.

Mechanism of lncRNA SNHG19 miR-299-5p MAPK6 signaling axis promoting metastasis of non-small cell lung cancer cells

Objective The aim of this study was to explore the mechanism behind lncRNA small nucleolar RNA host gene 19(lncRNA SNHG19)/microrNA-299-5P(miR-299-5p)/mitogen-activated protein kinase 6(MAPK6)signaling axis promoting metastasis of non-small cell lung cancer(NSCLC).Methods To analyze the abnormal expression of lncRNAs in NSCLC,50 surgically resected NSCLC and adjacent tissue samples were collected from August 2021 to August 2022.The mRNA expression levels of lncRNA SNHG19,Mir-299-5p,and MAPK6 were detected by qRT-PCR.The functions of lncRNA SNHG19,Mir-299-5p and MAPK6 were investigated by CCK-8,clone formation,EdU,scratch,Transwell western blotting(WB)and in vivo xenograft assay.RNA fluorescence in-situ hybridization(FISH),RNA pull-down,dual luciferase reporter,and RNA co-immunoprecipitation assays were used to explore the mechanism of action between lncRNA SNHG19,miR-299-5p,and MAPK6.Results High expression of lncRNA SNHG19 was correlated with poor prognosis,tumor size,lymph node metastasis,and TNM stage in NSCLC patients(P<0.05).Cell function experiments showed that lncRNA SNHG19 could improve the proliferation,clone formation,migration,and invasion ability of A549 cells both in vitro and in vivo(all P<0.05)and increased the relative expression levels of vimentin and MAPK6(P<0.05).The relative expression level of E-cadherin was decreased(P<0.05).lncRNA SNHG19 can interact with Mir-299-5p and regulate the expression level of MAPK6.Conclusion lncRNA SNHG19 is upregulated in NSCLC tissues and cells,and its high expression is associated with tumor progression and poor survival.Moreover,it can act as a molecular sponge for Mir-299-5p to regulate MAPK6 expression and promote the proliferation and metastasis of A549 cells.

CYFRA 21-1 as an early predictor of first line chemotherapy response in advanced non small cell lung cancer

Objective： In an era of ever evolving, promising new therapies for advanced non small cell lung cancer （NSCLC）, early predictors of response to therapy, are needed. We evaluated early variations in CYFRA 21-1 serum levels of patients with advanced NSCLC receiving first line chemotherapy and correlated the results with objective tumor response. Methods： 29 consecutive, previously untreated, patients of advanced non small cell lung cancer, with measurable disease on CT scan were evaluated. All patients were treated with conventional systemic chemotherapy, although the choice of chemotherapy was left to the discretion of the treating physicians. Serum samples were obtained immediately before the start of 1st and 2nd cycles of chemotherapy. CYFRA 21-1 was measured with an electrochemiluminescense immunoassay on an automatic analyzer （Elecsys 2000; Roche Diagnostics）. Response was evaluated using Response evaluation criteria in solid tumors （RECIST） criteria. Results： 10 patients had partial response, 9 patients had stable disease and 9 had progressive disease. None of the patients had complete response. 21/29 （72%） patients had an elevated baseline value of CYFRA 21-1.62% patients （18/29） had a decrease in CYFRA 21-1 after 1 cycle of chemotherapy. The average reduction in the 2nd reading was irrespective of whether baseline value was normal or not. The average reduction was statistically significant （P = 0.002; 95% CI, from 0.8369 to 3.49464; t test）. 8 out of 10 （80%） patients with partial response had a reduction in their 2nd reading of. CYFRA （P = 0.019; 95% CI, from 0.81965 to 7.20035; t test） which was significant. We also observed that 6/9 （66%） patients whose disease remains stable also had a decrease in their subsequent reading （P = 0.0106; 95% CI, from -0.44942 to 3.82720; t test）, though it was not significant statistically. Although 5 out of 9 （55%） patients, who had an increase in their CYFRA 21-1 level, had progressive disease, but it was not statistically significant （P = 0.537; 95% CI, from -1.20021 to 2.13354; ttest）. 14 out of 19 （73%） who either had partial response or had stable disease, had a reduction in their 2nd value of CYFRA 21-1 and was significant statistically （P = 0.004; 95% CI, from 0.74792 to 3.50208; t test）. We also observed that except for 1 patient, all patients who had a decrease of 42% or more in their subsequent CYFRA 21-1 level, were those who had either responded to chemotherapy or had stable disease （P = 0.001）, which was statistically significant. Conclusion： We can conclude that monitoring of serum marker CYFRA 21-1, early dudng first-line chemotherapy may be a useful prognostic tool for evaluation of early tumor response in patients with advanced NSCLC.

Diagnostic value of tumor marker pro-gastrin-releasing peptide in patients with small cell lung cancer： a systematic review

Background Lung cancer is one of the most common malignancies in the world and one of the leading cancers that result in death. The aim of this study was to evaluate and compare the diagnostic value of the serum tumor marker pro-gastrin-releasing peptide 31-98 （ProGRP31-98） to pathological diagnosis as reference standard in patients with suspected small cell lung cancer （SCLC）.Methods Literature searches covering 1978 through to 2009 were performed in Pubmed, OVID, MEDLINE, EMbase,Cancerlit, China National Knowledge Infrastructure （CNKI）, and CBM using the key search words; ＇small cell lung cancer＇,＇tumor marker＇, ＇ProGRP31-98＇ and ＇diagnostic tests＇, ＇ELISA＇, ＇EIA＇ and ＇diagnostic accuracy＇. Studies were collected and data analyzed to evaluate the diagnostic value of serum ProGRP31-98 levels for the diagnosis of SCLC compared with pathology. Eligibility criteria for inclusion in the analysis were based on criteria for diagnostic research published by the Cochrane Screening and Diagnostic Tests Methods Group （SDTMG）. The characteristics of the included articles were appraised and the data were extracted from the original articles for further statistical analysis of study heterogeneity using Review Manager 4.2 software. Based on study heterogeneity analysis, a suitable ＇effect＇ model was selected to calculate pooled sensitivity and specificity by meta-analysis. A Summary Receiver Operating Characteristic （SROC） curve and the area under the curve （AUC） were generated and sensitivity analysis conducted.Results A total of 22 articles were entered into this meta-review, including 11 English articles with a quality at level C. In total, the studies involved 6759 subjects, of which 1470 were diagnosed with SCLC by pathology, and 5289 subjects diagnosed with non-SCLC （NSCLC）. The meta-analysis showed that heterogeneity among studies was high （P=0.00001,（I2）=86.8%）. With ELISA, the pooled sensitivity was 0.72 （0.70 to 0.75 at 95% Cl） and the pooled specificity was 0.93 （0.92to 0.94 at 95% Cl）; the SROC and the AUC were 0.8817. These data suggest that ProGRP31-98 has a relatively high rate of missed diagnosis （28%）, but a relatively low rate of misdiagnosis （7%）.Conclusion From meta-analysis, we concluded that serum ProGRP31-98 is a valuable marker with a high specificity for diagnosis of SCLC with a similar diagnostic accuracy to pathology.

Preliminary radioimmunoimaging and biodistribution of ^131iodine-labeled single-chain antibody fragment against progastrin-releasing peptide（31-98） in small cell lung cancer xenografts

Background Monoclonal antibodies （mAbs） such as DD3,raised against progastrin-releasing peptide（31-98） （ProGRP（31-98）） antigen,have been used to target small cell lung cancer （SCLC）.However,as an intact mAb,DD3 is cleared slowly from the body,with an optimal radioimmunoimaging time of 72 hours.More recently,a singlechain antibody fragment has demonstrated reduced excretion time in blood and normal tissues and is increasingly used in diagnostic cancer research.Thereby,it potentially increases the radioimmunoimaging efficacy.However,there have been few studies with this antibody fragment.The aim of this study was to characterize the preliminary radioimmunoimaging and biodistribution of 1311I-anti-ProGRP（31-98）scFv in nude mice bearing SCLC xenografts.Methods Anti-ProGRP（31-98） scFv was used to detect ProGRP expression by flow cytometry analysis and immunohistochemistry.131I-anti-ProGRP（31-98） scFv was injected intravenously into healthy Kunming mice and the percentage injected dose per gram （%ID/g） in various organs was calculated.Similarly,the %ID/g and tumor/non-tumor ratio in xenograft-bearing mice was calculated.After injection of 131I-anti-ProGRP（31-98） scFv,treated mice were imaged at 1,24,and 30 hours.Then the tumor/base ratios were calculated.Results ProGRP was highly expressed in NCI-H446 cells and xenograft tissue.The metabolism of 131I-anti-ProGRP（31-98） scFv in healthy mice was consistent with a first-order and two-compartment model; T1/2α and T1/2β were 10.2 minutes and 5 hours 18 minutes,respectively.The %ID/g of 131I-anti-ProGRP（31-98） scFv in xenografts was much higher than in healthy tissues at 12 hours after injection,reaching a maximum of （5.38±0.92） %ID/g at 24 hours.Successful imaging of xenograft tissue was achieved as early as 1 hour post-injection and persisted until 30 hours,with 24 hours proving optimal.Conclusion 131I-anti-ProGRP（31-98）scFv shows highly selective tumor uptake with low accumulation in normal tissues and rapid blood clearance,indicating thatit could be a promising agent for SCLC radioimmunoimaging.

非小细胞肺癌的化疗进展

在中国,非小细胞肺癌是最常见的癌症致死原因之一,发病率也居高不下。诊断时,大部分病期晚,手术、放疗、化疗的远期获益有限。然而,新近有关化疗的临床试验却在不断的取得进展。本文综述非小细胞肺癌的辅助、新辅助、一线、二线化疗、老年或行为状态差的患者化疗进展。

广泛期小细胞肺癌一线化疗进展

小细胞肺癌(small cell lung cancer,SCLC)生长迅速,具有高度的侵袭性,就诊时多数患者已发生远处转移,对于广泛期小细胞肺癌,治疗仍以全身化疗为主,在过去30余年里,EP/CE方案作为标准一线化疗方案在治疗广泛期小细胞肺癌中取得了较高的缓解率,但多数患者在化疗停止6个月内疾病发生进展,2年的生存率不足5%,我们需要更加积极有效的一线化疗方案,本文综述了近10余年来广泛期小细胞肺癌的一线化疗进展。

手术联合拓扑替康、顺铂化疗治疗小细胞肺癌的疗效

目的:回顾性总结及评价金喜素(拓扑替康)、顺铂化疗与手术综合治疗35例小细胞肺癌(SCLC)的疗效。方法:35例SCLC患者,II期9例(20.5%),IIIA期26例(79.5%),术前均用金喜素、顺铂化疗两个疗程后行肺癌根治手术,术后化疗3个疗程以上,对术后满1年半35例和术后满3年18例进行随访,分别观察1年半和3年生存率。结果:35例1年半生存率为94.2%;18例3年生存率为83.3%。结论:金喜素、顺铂化疗和手术外科联合治疗对IIIA分期以内的SCLC具有良好的治疗效果。