Alterations and Its Mechanisms of Wnt Signal Pathway in Human High-matastatatic Large Cell Lung Cancer Cell Line L9981 by Transfecting with Nm23-H1 Gene

Backgroud and Objective Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the

The Expression Levels of KAI1 Gene and Its Mechanism in Human Lung Cancer Cell Lines

Background and Objective Lung cancer is one of the most malignant cancers which is hazarding the people’s health and life in the world. In the past half century, the incidence and mortality

Alterations in the Cytoskeleton and Biological Behavior in Human Lung Cancer Cell Line L9981 by Nm23-H1 gene Transfection

Objective and Methods The key cause of failure to cure and high mortality in lung cancer. At present, it has been known

Influence of Nm23-H1 Gene Site Mutagenesis on Invasive And Metastatic Phenotype in Human High-Metastatic Large Cell Lung Cancer Cell Line L9981

Background and Objective Invasion and metastasis is not only the malignant phenotypes of lung cancer but also the main cause of death. To study and elucidate the molecular mechanism

Screening and Verifying of Metastasis-associated Genes of Human Lung Cancer Cell Lines with Different Metastatic Potential

Background and Objective Lung cancer is the most lethal malignangy that threatens human health and lives nowadays in the world, The overall cure rate of lung cancer is only 13% -15%,

Effects of Methylseleninic Acid on the Proliferation and Cell Cycle in Human High Metastatic Large Cell Lung Cancer Cell Line L9981 and Its Molecular Mechanism

Background and Objective Lung cancer is the rst killer of human being in the whole world. Recently, although many treatment strategies have been developed, the anti-cancer effects

THE EFFECTS OF THE ETHANOLIC FRACTION OF CORIOLUS VERSICOLOR ON THE A549 NON-SMALL-CELL LUNG CANCER CELL LINE

Coriolus versicolor has demonstrated anti-cancer effects via polysaccharide-peptides(PSP)and polysaccharide Krestin(PSK).However,many other bioactive compounds within Coriolus versicolor(CV)may not have been identified.Our primary focus was to determine whether the ethanolic extract of Coriolus versicolor demonstrated any anti-cancer effects.The crude ethanolic extract was utilized,as was

Efficacy of gefitinib as a first-line single agent treatment in patients with advanced non-small cell lung cancer

Objective： To assess the efficacy and toxicity of gefitinib as a single agent treatment in Chinese patients with advanced non-small cell lung cancer （NSCLC）. Methods： Forty-five patients with advanced NSCLC were treated with gefitinib at 250 mg daily until the disease progressed or the patient could not tolerate the toxicity. Results： None of the patients achieved a complete response （CR）, while 15 patients achieved a partial remission （PR） and 17 experienced a stable disease （SD）. Thirteen patients continued to have a progressive disease （PD）. The response rate and the disease control rate were 33.3% and 71.1%, respectively. The symptom remission rate was 72.5%, and the median remission time was 8 days. The median survival time was 15.3 months. The median progression-free survival time was 6.0 months. The most common toxicities included rash （53.3%） and diarrhea （33.3%）. Dehydration and pruritus of the skin developed in 26.7% and 22.2% of the patients, respectively. Hepatic toxicity occurred in 6.7% of patients and oral ulceration occurred in 4.4% of patients. Conclusion： Single agent treatment with gefitinib is effective against advanced NSCLC, and is well tolerated in Chinese patients.

The Difference of the Copy Number Variation and Loss of Heterozygosity of Human Lung Large Cell Cancer Cell Line with Different Metastatic Potential

Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by

Weekly albumin-bound paclitaxel/cisplatin versus gemcitabine/cisplatin as first-line therapy for patients with advanced non-small-cell lung cancer:A phase II open-label clinical study

Objective: The aim of this trial was to compare both the efficacy and the safety of a weekly nanoparticle albumin-bound paclitaxel(nab-paclitaxel) plus cisplatin vs. gemcitabine plus cisplatin in patients with advanced non-small-cell lung cancer(NSCLC).Methods: A total of 84 participants received either 100 mg/m^2 nab-paclitaxel each week on d 1, 8 and 15 of a 28 day cycle, as well as cisplatin 75 mg/m^2 on d 1 every three weeks(nab-TP arm); or gemcitabine 1,000 mg/m^2 on d 1 and 8, plus cisplatin 75 mg/m^2 on d 1 every three weeks(GP arm). The primary end point was progression-free survival(PFS). The secondary end points were overall response rate(ORR) and overall survival(OS).Results: According to our analysis, the median PFS was 4.8 months for the nab-TP arm vs. 5.2 months for the GP arm(P=0.55). Analysis showed the median OS was 14.6 months for participants who were in the nab-TP arm vs. 15.1 months for those in the GP arm(P=0.94). Besides, nab-TP showed OS advantages over GP in patients harboring epidermal growth factor receptor(EGFR) mutation(26.7 vs. 15.3 months, P=0.046) and patients with a performance status of 0(23.5 vs. 14.7 months, P=0.020). It was found that incidences of drug-related grade 3 or 4 toxicities were comparable between the two treatment arms.Conclusions: Therefore, it can be seen that weekly nab-TP treatment has a similar efficacy and tolerability to GP treatment for patients who are undergoing their first-line treatment for NSCLC. It could be that survival differences among platinum doublets in the context of both EGFR mutation and performance status have the potential to be the basis for our further clinical trials.

Safety and Efficacy of Racotumomab-Alum Vaccine as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer

Despite extensive clinical research in non-small cell lung cancer (NSCLC), overall survival is still poor. Racotumomab-alum is an anti-idiotypic cancer vaccine that targets NeuGcGM3 tumor associated ganglioside. The aim of this study was to evaluate safety and efficacy of racotumomab-alum in advanced NSCLC patients with progressive disease. This expanded access program included 86 histologically confirmed NSCLC patients, 18 years or older age, with advanced disease and without therapeutic option, with ECOG performance status ≤3, adequate organ functions and signed informed consent. The primary endpoint was overall survival and toxicity was measure assessed treatment-related toxicity according CTCAEv3. The study was approved by ethical review boards of participant institutions. Racotumomab-alum treatment consisted in 5 biweekly intradermal doses (1 mg/mL) during the induction phase of treatment (2 months). The maintenance phase consisted in monthly re-immunizations until unacceptable toxicity or PS worsening. The median overall survival time of all patients treated with racotumomab-alum was 8.96 months. The survival rates at 12 and 24 months were 42.8% and 28.0%, respectively. Patients that completed the induction phase of treatment (five doses or more) reached a median OS of 12.1 months. The most common adverse events were injection site reaction, bone pain, cough and asthenia. Racotumomab-alum cancer vaccine could be considered an effective and safe treatment option as second-line therapy for advanced NSCLC. Further clinical studies should be conducted to confirm this result.

INFLUENCE OF ZINC，MANGANESE AND SELENIUM ONSUPEROXIDE DISMUTASE ACTIVITY IN LUNGCANCER TISSUE AND CELL IN CULTURE

In this experiment,the cancer tissues and cells,Which were derived from Lewis lung cancer and A549 lung Cancer cell line,were respectively divided into four groups and zinc, manganese and selenium were respectively added to the medium for 24 hours. The superoxide dismutase activity in the tissues and the cells was estimated. It was found that the SOD activity was enhanced by zinc and manganese and the effect of zinc on SOD activity was superior to that of manganese. We supposed that the enhance of the SOD activity was relative to the activation of the SOD apoenzymes. This experimental result indicated that the inhibitory effect of zinc and manganese on carcinogenesis was achieved by SOD and the elements might be considered a SOD activator.

Transfection of Nm23-H1 Gene Inhibited the Metastatic Potential of Human High-metastatic Large Cell Lung Cancer L9981

Background and objective Invasion and metastasis is not only the malignant phenotypes of lung cancer but also the main cause of death. Elucidating the molecular mechanism of

Prognostic factors of refractory NSCLC patients receiving anlotinib hydrochloride as the third-or further-line treatment

Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.

奥希替尼联合化疗在伴有EGFR突变晚期非小细胞肺癌一线治疗中的应用

1文献来源Planchard D,Jänne PA,Cheng Y,et al.Osimertinib with or without chemotherapy in EGFR⁃mutated advanced NSCLC[J].N Engl J Med,2023,389(21):1935-1948.2证据水平1b。

XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer

Background X-linked inhibitor of apoptosis （XlAP）-associated factor 1 （XAF1） is a new tumor suppressor. Low expression of XAF1 is associated with poor prognosis of human cancers. However, the effect of XAF1 on lung cancer remains unknown. In this study, we investigated the expression of XAF1 and its role in squamous cell lung cancer. Methods Cancer tissues, cancer adjacent tissues and normal lung tissues were collected from 51 cases of squamous cell lung cancer. The expression of XAF1 mRNA was determined by reverse transcription-polymerase chain reaction （RT-PCR）. The expression of XAF1 protein was determined by Western blotting and immunohistochemical staining. Ad5/F35-XAF1 virus was generated. Cell proliferation and apoptosis were measured by 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） method and flow cytometry （FACS）, respectively. Results The levels of XAF1 protein and mRNA in cancer tissues were significantly lower than those in cancer adjacent and normal lung tissues （P 〈0.05）. The low expression of XAF1 was associated with tumor grade, disease stage, differentiation status and lymph node metastasis in squamous cell lung cancer patients. The restoration of XAF1 expression mediated by Ad5/F35-XAF1 virus significantly inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner. Conclusion XAF1 is a valuable prognostic marker in squamous cell lung cancer and may be a potential candidate gene for lung cancer therapy.

GRP78 upregulation-induced increase in cisplatin sensitivity of SPCA1 lung cancer cells

Background Glucose regulated protein 78 （GRP78）, an endoplasmic reticulum （ER） chaperone, plays a critical role in chemotherapy resistance in a variety of cancers. In this study, we investigated the up-regulation of GRP78 induced by A23187 and its association with the chemotherapeutical sensibility to cisplatin in human lung cancer cell line SPCAI. Methods SPCA1 cells were pretreated with A23187 at different concentrations. The expression of GRP78 at the mRNA level was analyzed by RT-PCR; the expression of GRP78 at the protein level was determined by Western blotting and immunofluorescence assay. Cell survival was determined by MTT assay. Cell apoptosis was analyzed by flow cytometry. Results The expression of GRP78 at both the mRNA and protein levels was obviously induced by A23187 in SPCA1 cells, with an elevation of GRP78 by 2.1-fold at the mRNA level and by 3.8-fold at the protein level compared to the control. There was a dose-dependent response. Survival curve analysis demonstrated that A23187 induction caused a significant reduction of survival for the cells subjected to cisplatin treatment （P 〈0.05）. After treatment by cisplatin, the percentage of apoptotic cells in the A23187 pretreated group increased about three fold compared with the control group （（27.53!-4.32）% vs. （9.25＋3.64）%, P 〈0.05）. Conclusions A23187 treatment was fairly effective for the induction of GRP78 in SPCA1 cells at both the mRNA and protein levels. To a certain extent, GRP78 up-regulation by A23187 was associated with the enhancement of drug sensitivity to cisplatin in human luncl cancer cell line SPCAI.

安罗替尼联合一线化疗治疗晚期非小细胞肺癌的效果

目的研究安罗替尼联合化疗一线治疗晚期非小细胞肺癌(NSCLC)的价值。方法回顾分析2018年3月至2022年5月郑州大学第五附属医院收治的90例晚期NSCLC患者资料,其中45例接受单纯一线化疗的患者纳入对照组,45例联合安罗替尼治疗的患者纳入观察组。两组均连续治疗4个化疗周期。记录两组治疗效果、肿瘤标志物水平[细胞角蛋白19片段抗原21-1(CYFRA21-1)、癌胚抗原(CEA)和神经元特异性烯醇化酶(NSE)]、生存情况、不良反应发生情况。结果治疗后,观察组治疗总有效率高于对照组(P<0.05)。治疗前,两组CYFRA21-1、NSE、CEA差异无统计学意义(P>0.05);治疗后,两组CYFRA21-1、NSE、CEA均降低,且观察组低于对照组,差异有统计学上的意义(P<0.05)。观察组生存时间长于对照组,生存率高于对照组,差异有统计学上的意义(P<0.05)。治疗期间,两组不良反应发生率差异无统计学意义(P>0.05)。结论安罗替尼联合化疗一线治疗晚期NSCLC可以进一步提高效果,降低肿瘤标志物水平,有助于延长患者生存时间,且不会增加不良反应,安全性较好。

替雷利珠单抗一线治疗晚期非小细胞肺癌的快速卫生技术评估

目的评价替雷利珠单抗(TIS)一线治疗晚期非小细胞肺癌(NSCLC)的有效性、安全性和经济性。方法计算机检索PubMed、Embase、Cochrane Library、CNKI、WanFang Data、SinoMed数据库和卫生技术评估(HTA)相关网站,搜集TIS一线治疗晚期NSCLC的HTA报告、系统评价/Meta分析和药物经济学研究,检索时限均从建库至2024年4月30日。由2名研究者独立筛选文献、提取资料和质量评价,并采用定性描述方法进行快速卫生技术评估。结果共纳入9篇文献,包括系统评价/Meta分析7篇,药物经济学研究2篇。有效性方面,与化疗(CT)相比,TIS+CT可提高晚期NSCLC患者的无进展生存期(PFS)和客观缓解率(ORR),可提高任何程序性细胞死亡受体配体-1(PD-L1)表达情况、伴或不伴肝转移、年龄≥65岁或<65岁、有吸烟病史的晚期NSCLC患者的PFS;与CT相比,TIS+CT可提高晚期非鳞状NSCLC患者的PFS,可提高PD-L1≥50%的晚期非鳞状NSCLC患者的PFS;与CT相比,TIS+CT可提高PD-L1为1%~49%、PD-L1≥50%、男性、年龄≥65岁、有吸烟史、ECOG评分1分、ⅢB期和Ⅳ期晚期鳞状NSCLC患者的PFS。安全性方面,与卡瑞利珠单抗+CT和阿替利珠单抗+贝伐珠单抗+CT相比,TIS+CT可降低严重不良反应发生率。经济学方面,对于无表皮生长因子受体突变和渐变淋巴瘤激酶重排的非鳞状NSCLC,与CT相比,TIS+CT在中国具有一定的成本-效果优势。亚组分析结果显示,在PD-L1表达≥50%、肝转移和有吸烟史的非鳞状NSCLC患者中,一线TIS+CT方案的生存益处更大。结论TIS+CT一线治疗晚期NSCLC具有较好的有效性、安全性和经济性。

TGF-β/Akt/Smad signaling regulates ionizing radiation-induced epithelial-mesenchymal transition in acquired radioresistant lung cancer cells

Objective:To define the properties of lung cancer cells that resisted conventionally fractionated radiation exposure.Methods:Acquired radioresistant lung cancer cell line A549 was constructed by X-ray irradiation with a clinical conventional fraction dose of 2 Gy daily during 30 fractions.Cell morphology,molecular markers,migration capacity and invasion potential were evaluated by the microscope,Western blot,immunofluorescence,wound healing test and transwell chamber assay,respectively.Results:Radioresistant A549 cells shifted from an epithelial to a mesenchymal morphology,termed as epithelial-mesenchymal transition(EMT),and was accompanied by decreased expressions of epithelial markers(F=4.568,P<0.05)and increased expression of mesenchymal markers(F=4.270,P<0.05),greater migratory and invasive capabilities(t=6.386,5.644,P<0.05).The expression of TGF-β,and phosphorylated levels of Akt and Smad3 were also enhanced(F=6.496,4.685,3.370,P<0.05).Furthermore,the EMT phenotype induced by radiation could be reversed through inhibition of TGF-β,Akt or Smad3,indicating a functional relationship be-tween them.Conclusions:EMT mediates acquired radioresistance of lung cancer cells induced by IR with clinical parameters,and the crosstalk mode of TGF-β/Akt/Smad signaling plays a critical regulatory role in this process.