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

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%,

The pooled analysis of single gemcitabine for non-small cell lung cancer patients with elderly age

Objective:Gemcitabine,used as single agent for elderly patients with non-small cell lung cancer (NSCLC),was demonstrated effective in this population based on phase II studies.The aim of this study was to summarize all those phase II studies with the hope to get a comprehensive understanding of gemcitabine efficacy.Methods:The PubMed database was used to search all the papers on NSCLC associated with gemcitabine used as single agent in the first line setting till to March 31st,2010.And the medians and their 95% CI of overall response rate (ORR),disease control rate (DCR),progression free survival (PFS),and overall survival (OS) were calculated.Results:1.There were 7 papers including 410 patients with performance status (PS) ≤ 2 and advanced stage collected.2.The dose-intensities of gemcitabine were 843.75 mg/m 2 /week-1125 mg/m 2 /week in the 4-week schedule,and 666.7 mg/m 2 /week in the 3-week schedule.3.The median age was 73.8 (95% CI was 72.44,75.16) years old;36.1% (95% CI:31.4%,40.7%) of patients with stage IIIB and 60.5% (95% CI:55.8%,65.2%) of patients with stage IV;35.9% (95% CI:31.2%,40.5%) patients were adenocarcinomas and 43.7% (95% CI:38.9%,48.5%) patients were squamous cell carcinomas (SCCs).4.The ORR,DCR,PFS/TTP,and OS were 22.3% (95% CI:18.2%,26.5%),58.4% (95% CI:53.5%,63.4%),3.6 (95% CI:2.9,5.15) months and 6.68 (95% CI:5.4,8.11) months,respectively.Conclusion:Gemcitabine as single agent applied in this special population was effective and can be well tolerated under different doses and usage.

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.

Short-term outcomes of cetuximab combined with standard chemotherapy as non-first line setting for patients with non-small cell lung cancer:a report of 6 cases

Objective:Cetuximab combined with chemotherapy has been used to treat non-small cell lung cancer (NSCLC) in recent years, most of them were first line setting.This study was to summarize our experiences in treating NSCLC patients with cetuximab in the non-first line setting.Methods:From October 1st 2006 to December 31st 2009, six NSCLC patients were treated with cetuximab combined standard chemotherapy as non-first line setting in Sun Yat-sen University Cancer Center, China.The short-term efficacies and safeties were analyzed.Results:1.A total of 18 cycles of cetuximab treatment, with a median of two cycles in the whole group.2.There were 6 patients treated as non-first line setting, overall response rate (ORR) was 33.3% (2/6), disease control rate (DCR) was 33.3% (2/6), median time to progression (TTP) was 3.5 (3-4) months, and median OS was 18 (4-28) months.3.There were 50% (3/6) patients occurred acne-like rash within three weeks, their ORR was 66.7% (2/3), and DCR was 66.7% (2/3), however, both of ORR and DCR in patients who didn't occurred acne-like rash were 0% (0/3), the differences of ORR, DCR between two groups were in significant different (P=0.143).4.There was no treatment-associated death and no cetuximab-associated discontinuation.The incidence of acne-like rash was 50% occurred within three weeks, there were two patients suffered side effects associated with chemotherapy.Conclusion:The data of cetuximab application in non-first line setting for patients with NSCLC were rare, and the addition of cetuximab in those population was safe.

Effects of chimeric intron on the epithelial-mesenchymal transformation of non-small cell lung cancer PC-9

Objective:To investigate the effects of Intron on the EMT capability of non-small cell lung cancer cell line PC-9.Methods:Firstly,using the psiCHECK-2 plasmid as a basic framework to construct the recombinant plasmid of psiCHECK-2-Intron dual-luciferase reporter gene;secondly,the psiCHECK-2-Intron and psiCHECK-2 were transfected into PC-9 cells respectively.The migration and invasion abilities of PC-9 cells were analyzed by Matrigel assay.The expression changes of EMT related hallmarks,including N-cadherin,β-catenin and snail,were detected by qRT-PCR and Western Blotting.Results:Compared with the control group,the migration and invasion abilities of PC-9 cells in Intron group significantly decreased(p<0.001).The expression of N-cadherin,β-catenin and snail also down-regulated(p<0.001).Conclusion:The introns could inhibit the EMT of PC-9 cells.

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.

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

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

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

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

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 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

Anti-tumor Effect of Newcastle Disease Virus Expressing IL-2 in Lung Cancer Model

Recombinant Newcastle disease virus(rNDV)has shown an anti-cancer effect in preclinical studies,but has never been tested for lung cancer models.This study explored the anti-cancer activity of genetically modified NDV expressing IL-2(rNDV–IL-2)in lung cancer models.This study used Lewis lung carcinoma cell line(LLC)to create tumor models in C57 female mice,the tumor-bearing mice were treated with rNDV-IL-2,rNDV and phosphate-buffered saline(PBS),respectively.In vitro results revealed that rNDV effectively infected malignant cells and expressed IL-2,in vivo results revealed that rNDV expressing IL-2 was highly efficient in inhibiting lung cancer tumors,with an average tumor size of 291.255 mm^3 in rNDV-IL-2 group compared to 763.068 mm^3 in rNDV group and 1101.68 mm^3 in PBS group.For the survival studies,treatment with rNDV-IL-2 enhanced the survival rates of tumor-bearing mice by 36%compared to those of rNDV treated mice and by 80%compared to those of vehicle-treated mice(survival rate:12 out of 15 for rNDV-IL-2 group;seven out of 15 for rNDV group and zero out of 15 for vehicle group).These results demonstrated that rNDV-expressed IL-2 enhanced the intrinsic anti-tumor ability of Newcastle disease virus in lung cancer models by further restrain of lung tumor growth and improvement of the survival rates of the tumor-bearing mice.The genetically modified rNDV-IL-2 was a good candidate for lung cancer therapy.

ANTI-HUMAN LUNG GIANT CELL CANCER (PG) EFFECT OF HUMAN LAK CELLS IN VITRO AND IN NUDE MICE

Human LAK cells were prepared by culturing normal human peripheral blood mononuclear cells (PBMC) with or without rIL-2 and assayed for T cell surface markers as well as anti-tumor activity against PC in vitro and in nude mice. Although the percentages of T3, T4, and T8 positive cells in rIL-2-activated cells did not differ significantly from those of control cells in vitro, the former showed stronger cytotoxicity than control cells to PG tumor cells in vitro. In vivo, LAK cells completely inhibited the growth of PG tumor in nude mice, whereas PBMC control cells were to be of no effect. The anti-tumor effect of human LAK cells in nude mice may offer a useful model to study the role of human LAK cells against human tumor in vivo.

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.

Epidermal growth factor receptor genotype in plasma DNA and outcome of chemotherapy in the Chinese patients with advanced non-small cell lung cancer

Background The genotype of epidermal growth factor receptor （EGFR） is associated with tyrosine kinase inhibitor and effectiveness of therapy, but its role in cytotoxic chemotherapy is still unknown. Previous studies indicated that certain EGFR mutations were associated with response and progression free survival following platinum based chemotherapy. Our recent studies have identified that EGFR genotypes in the tumour tissues were not associated with response to the first-line chemotherapy in Chinese patients with advanced non-small cell lung cancer （NSCLC）. In this study, we investigated associations of EGFR genotypes from plasma of patients with advanced NSCLC and response to first-line chemotherapy and prognosis. Methods We enrolled 145 advanced NSCLC patients who had received first-line chemotherapy in our department. We examined plasma EGFR genotypes for these patients and associations of EGFR mutations with response to chemotherapy and clinical outcomes. Results There were 54 patients with known EGFR mutations and 91 cases of wild types. No significant difference was detected in the response rate to first-line chemotherapy between mutation carriers and wild-type patients （37.0% vs. 31.9%）. The median survival time and 1-, 2-year survival rates were higher in mutation carriers than wild-types （24 months vs. 18 months, 85.7% vs. 65.7% and 43.7% vs. 25.9%, P=0.047）. Clinical stage （Ⅳvs. Ⅲb）, response to the first-line chemotherapy （partial vs. no） and EGFR genotype were independent prognostic factors. Conclusion Plasma EGFR mutations in the Chinese patients with advanced NSCLC is not a predictor for the response to first-line chemotherapy, but an independent prognostic factor indicating longer survival.

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.

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.