Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

Inhibitory Effect of MiR-449b on Cancer Cell Growth and Invasion through LGR4 in Non-Small-Cell Lung Carcinoma

Non-small-cell lung carcinoma （NSCLC） is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b （miR-449b） functions as a tumor suppressor in many cancers. However, the role of miR- 449b in NSCLC is still unknown. In the present study, miR-449b was significantly down- regulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3＇-UTR region of leucine rich repeat containing G protein-coupled receptor 4 （LGR4） mRNA had putative complementary sequences to miR-449b, which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.

Clinical Observation on Treatment of NonParvicellular Carcinoma of the Lung with Jin Fu Kang Oral Liquid

Jin Fu Kang Oral Liquid ([symbol: see text]), made of traditional Chinese drugs for supplementing qi and nourishing yin, was developed according to the common symptoms in lung carcinoma with deficiency of both qi and yin. Of the 96 cases in the Jin Fu Kang group, 1 case got complete remission (CR) after treatment, 8 cases partial remission (PR), 52 cases no change (NC), PR + NC covering 63.5%. Of the 52 cases in the group of Jin Fu Kang plus chemotherapy, 11 cases got PR after treatment, 26 cases NC, PR + NC covering 71.2%. Of the 25 cases in the chemotherapy group, 4 cases got PR after treatment, 11 cases NC, PR + NC covering 60.0%. The results show that the therapeutic effectiveness in the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy was better than that in the chemotherapy group. The one-year survival rate and the two-year survival rate after treatment in the Jin Fu Kang group were 67.3% and 67.3% respectively; 66.7% and 66.7% in the group of Jin Fu Kang plus chemotherapy; and 40.3% and 0.0% in the chemotherapy group. The improvement of clinical symptoms, increase of body weight and improvement of health situation (KPS marks) after treatment in both the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy were better than that in the chemotherapy group. Some indicators of immunology and hemogram after treatment were greatly improved in the Jin Fu Kang group, worse in the chemotherapy group, but no obvious improvement in the group of Jin Fu Kang plus chemotherapy.

Pembrolizumab-emerging treatment of pulmonary sarcomatoid carcinoma: A case report

BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.

Pang Fuwan Uses Yao Medicine to Observe the Therapeutic Effects on the Physical and Mental Symptoms of Patients with Advanced Non-Small Cell Lung Cancer

Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.

Unresectable stage Ⅲ non-small-cell lung cancer: Have we made any progress?

Lung cancer is responsible for the most cancer deaths worldwide with an incidence that is still rising. One third of patients have unresectable stage ⅢA or stage ⅢB disease. The standard of care for locally advanceddisease in patients with good performance status consists of combined modality therapy in particular concurrent chemoradiotherapy. But despite a lot of efforts done in the past, local control and survival of patients with unresectable stage Ⅲ non-small-cell lung cancer(NSCLC) remains poor. Improving outcomes for patients with unresectable stage Ⅲ NSCLC has therefore been an area of ongoing research. Research has focused on improving systemic therapy, improving radiation therapy or adding a maintenance therapy to consolidate the initial therapy. Also implementation of newer targeted therapies and immunotherapy has been investigated as well as the option of prophylactic cranial irradiation. This article reviews the latest literature on improving local control and preventing distant metastases. It seems that we have reached a plateau with conventional chemotherapy. Radiotherapy dose escalation did not improve outcome although increasing radiation dose-intensity with new radiotherapy techniques and the use of newer agents, e.g., immunotherapy might be promising. In the future well-designed clinical trials are necessary to prove those promising results.

Apoptosis of Lewis Lung Carcinoma Cells Induced by Microwave via p53 and Proapoptotic Proteins In vivo

Background： Microwave therapy is a minimal invasive procedure and has been employed in clinical practice for the treatment of various types of cancers. However, its therapeutic application in non-small-cell lung cancer and the underlying mechanism remains to be investigated. This study aimed to investigate its effect on Lewis lung carcinoma （LLC） tumor in vivo. Methods： Fifty LLC tumor-bearing C57BL/6 mice were adopted to assess the effect of microwave radiation on the growth and apoptosis of LLC tumor in vivo. These mice were randomly assigned to 10 groups with 5 mice in each group. Five groups were treated by single pulse microwave at different doses for different time, and the other five groups were radiated by multiple-pulse treatment of a single dose. Apoptosis of cancer cells was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Western blotting was applied to detect the expression of proteins. Results： Single pulse of microwave radiation for 5 min had little effect on the mice. Only 15-min microwave radiation at 30 mW/cm2 significantly increased the mice body temperature （2.20 ± 0.82）℃ as compared with the other groups （0.78 ± 0.29 ℃, 1.24 ± 0.52 ℃, 0.78 ± 0.42 ℃, respectively）, but it did not affect the apoptosis of LLC tumor cells significantly. Continous microwave radiation exposure, single dose microwave radiation once per day for up to seven days, inhibited cell division and induced apoptosis of LLC tumor cells in a dose- and duration-dependent manner. It upregulated the protein levels of p53, Caspase 3, Bax and downregulated Bcl-2 protein. Conclusions： Multiple exposures of LLC-bearing mice to microwave radiation effectively induced tumor cell apoptosis at least partly by upregulating proapoptotic proteins and downregulating antiapoptotic proteins. Continuous radiation at low microwave intensity Ibr a short time per day is promising in treating non-small-cell lung cancer.

The Therapeutic Effects of the Radiotherapy Plus TCM Treatment Observed in Senile Non-Parvicellular Lung Cancer Patients at the Late Stage

47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.The patients in the treatment group orally took Chinese medicine during and after the radiotherapy.There was no obvious difference in short-term therapeutic effects between the two groups,but the long-term curative effects in the treatment group was obviously superior to that in the control group (P<0.05 or P<0.01).Conclusion:radiotherapy plus TCM can prolong the survival period for senile non-parvicellular lung cancer patients.

Molecular Mechanisms Contributing to Resistance to Tyrosine Kinase-Targeted Therapy for Non-Small Cell Lung Cancer

One of the most important pathways in non-small cell lung cancer(NSCLC) is the epidermal growth factor receptor(EGFR) pathway. This pathway affects several crucial processes in tumor development and progression,including tumor cell proliferation,apoptosis regulation,angiogenesis,and metastatic invasion.Targeting EGFR is currently being intensely explored.We are witnessing the development of a number of potential molecular-inhibiting treatments for application in clinical oncology.In the last decade,the tyrosine kinase(TK) domain of the EGFR was identified in NSCLC patients,and it has responded very well with a dramatic clinical improvement to TK inhibitors such are gefitinib and erlotinib.Unfortunately,there were primary and/or secondary resistance to these treatments,as shown by clinical trials.Subsequent molecular biology studies provided some explanations for the drug resistance phenomenon.The molecular mechanisms of resistance need to be clarified.An in-depth understanding of these targeted-therapy resistance may help us explore new strategies for overcoming or reversing the resistance to these inhibitors for the future of NSCLC treatment.

Value of COX-2 and HER-2 in Judging Condition and Prognosis in Non-Small Cell Lung Cancer Patients

OBJECTIVE To investigate the expressions of cyclooxygenase 2 （COX-2） and human epidermal growth factor receptor-2 （HER-2） in non-small cell lung cancer （NSCLC） and their clinical significance in identifying the progression and prognosis of the NSCLC patients. METHODS Immunohistochemical indirect method was used to detect the expressions of the COX-2 and HER-2 protein in 54 NSCLC specimens, 16 paraneoplastic specimens, and 10 normal tissue specimens. RESULTS The positive rates of COX-2 and HER-2 protein expressions were respectively 75.9% and 40.7% in the NSCLC specimens, 25% and 12.5% in the paraneoplastic specimens, and 0 in the normal tissue. The COX-2 protein expression in lung cancer （LC） was not only related to the smoking habit of the patients and histological grades of LC, but also to the TNM stages, and lymphatic metastasis （P 〈 0.05）. HER-2 protein expression closely correlated to the pathologic types, histological grades, TNM stages, and lymphatic metastasis （P 〈 0.05）. The result of univariate analysis showed that all the histological grades, TNM stages, lymphatic metastasis, and expressions of COX-2/HER-2 correlated to the prognosis of NSCLC patients （mean of P value 〈 0.01）. The multivariate survival analysis indicated that there were signi.cant di.erences in comparison of the survival time between the COX-2 （＋＋/＋＋＋） /HER-2 （＋＋/＋＋＋） and the COX-2 （-/＋）/HER-2 （-/＋） groups （P〈 0.001）, suggesting the COX-2/HER-2 was a negative prognostic factor. CONCLUSION COX-2 and HER-2 are valuable in identifying the progression of NSCLC and predicting the prognosis of NSCLC patients. COX-2 and HER-2 are useful for judging the NSCLC patient＇s condition, and are of great value to the decision of NSCLC prognosis.

Role of positron emission tomography-computed tomography in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell carcinoma and small cell carcinoma are the main histological subtypes and constitutes around 85% and 15% of all lung cancer respectively. Multimodality treatment plays a key role in the successful management of lung cancer depending upon the histological subtype, stage of disease, and performance status. Imaging modalities play an important role in the diagnosis and accurate staging of the disease, in assessing the response to neoadjuvant therapy, and in the follow-up of the patients. Last decade has witnessed voluminous upsurge in the use of positron emission tomography-computed tomography(PET-CT); role of PET-CT has widened exponentially in the management of lung cancer. The present article reviews the role of 18-fluoro-deoxyglucose PET-CT in the management of non small cell lung cancer with emphasis on staging of the disease and the assessment of response to neoadjuvant therapy based on available literature.

^(18)F-FDG uptake as a biologic factor predicting outcome in patients with resected non-small-cell lung cancer

Background The outcome of surgical treatment of non-small-cell lung cancer （NSCLC） remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. ^18F-fluoro-2-deoxy-glucose （^18F-FDG） uptake on positron-emission tomography （PET） is associated with the aggressiveness of NSCLC. The present study focused on the role of ^18F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC. Methods A retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value （SUVmax）, in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients＇ recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUVmax and other factors was also analyzed. Results Patients with SUVmax more than 11 had a disease-free survival and overall survival shorter than patients with SUVmax less than 11 in univariate analyses （P〈0.001, P=0.002）. In the multivariate analysis, SUVmax （dichotomized by 11） was the only significant predictor for tumor recurrence. TNM stage and SUVmax （dichotomized by 11） were independent predictors for the overall survival. Associations of SUVmax with p53 overexpression, proliferating cell nuclear antigen （PCNA） labeling index and microvascular density of the tumor were significant in the entire group. Conclusions ^18F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.

Effect of compound Kushen injection on T-cell subgroups and natural killer cells in patients with locally advanced non-small-cell lung cancer treated with concomitant radiochemotherapy

OBJECTIVE: To observe effect of compound Kushen injection on T-cell subgroups and NK cells in patients with locally advanced non-small-cell lung cancer(NSCLC) treated with concomitant radiochemotherapy.METHODS: We randomly divided 60 patients with locally advanced NSCLC who were treated at our hospital between May 2011 and May 2013 into a treatment group and a control group by drawing.The treatment group(n = 30) received concomitant radiochemotherapy plus compound Keshen injection, and the control group(n = 30) received only radiochemotherapy.RESULTS: After treatment, levels of CD3+, CD4+,CD4 +/CD8 + and CD16 +/CD56 + cells had significantly increased, and CD8 + cells had significantly decreased, in the treatment group compared with both their pretreatment levels and with levels in the control group. In the control group, post-treatment levels of CD3 +, CD4 +, CD4 +/CD8 + and CD16+/CD56+ cells were not significantly changed from pretreatment levels. The two groups did not significantly differ in their rates of toxicity reactions(P > 0.05).CONCLUSION: Compound Kushen injections can increase immunologic function in patients with locally advanced non-small cell lung cancer who receive concomitant radiochemotherapy.

Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer:protocol for a randomized double-blind controlled trial

BACKGROUND： Traditional Chinese medicine （TCM） is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer （NSCLC） are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC. METHODS AND DESIGN： This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles Progression-free survival （PFS） is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life （EORTC QLQ-LC43, and TCM syndrome score） Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed. DISCUSSION： Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC.

Integrated Chinese-western therapy versus western therapy alone on survival rate in patients with non-small-cell lung cancer at middlelate stage

OBJECTIVE: To compare the effects of integrated Chinese-Western therapy versus Western therapy alone on the survival rate of patients with non-small-cell lung cancer (NSCLC) at middle-late stage and to evaluate prognostic factors. METHODS: We selected 98 inpatients with middle-late stage NSCLC diagnosed from March 2009 to March 2011 and randomly divided them into two groups, with 49 cases in each group, and the clinical data were analyzed retrospectively.The control group was treated by the combined methods of Western Medicine, including chemotherapy, supportive treatment and symptomatic treatment. The observation group was treated by injection and prescriptions of Chinese medicine based on Traditional Chinese Medicine syndrome differentiation and by the same combined methods of western treatment used in the control group. After treatment, the survival rates of the patients were compared by the stage of cancer and evaluation of 24 prognostic factors analyzed by a Cox regressionmodel, and the clinical data were statistically analyzed. RESULTS: The survival rates of all patients were over 90.0% at 1 and 3 months after treatment with no significant differences between the two groups (P>0.05); In the observation group the survival rates at 6 months and 1 year were 93.4% and 42.8%, respectively, being superior to 85.6% and 18.3% in the control group (P<0.05). The median survival time in the observation group was superior to the control group (P<0.05); The effects of 24 prognostic factors were significantly better in the observation group than in the control group (P<0.05). CONCLUSION: Integrated Chinese-western therapy can significantly improve the survival rate in patients with middle-late stage NSCLC and improve prognostic factors compared with western therapy alone.

Effect of scar-producing moxibustion at the acupoints Zusanli(ST 36) and Feishu(BL 13) on neutrophil-to-lymphocyte ratio and quality of life in patients with non-small-cell lung cancer: A randomized,controlled trial

OBJECTIVE: To evaluate the effect of heat stimulation via scar-producing moxibustion at the acupoints Zusanli(ST 36) and Feishu(BL 13) on the neutrophil-to-lymphocyte ratio(NLR) and quality of life in patients with non-small-cell lung cancer(NSCLC).METHODS: Seventy patients with NSCLC were randomly assigned into two groups: group A received scar-producing moxibustion at the acupoints Zusanli(ST 36) and Feishu(BL 13) every day for 6 weeks, while group B received no intervention(control group). Outcome measures were the NLR and the scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30). The NLR and the EORTC QLQ-C30 were assessed at baseline and at the end of 6 weeks.RESULTS: Five participants dropped out, leaving afinal total of 65 participants who completed the trial. Groups A and B had a similar mean NLR at baseline. After the treatment course, the NLR in group A was significantly lower than that in group B(P <0.001). Compared with group B, the EORTC QLQ-C30 scores in group A were significantly greater in terms of global health status or quality of life(P < 0.001) and function(P < 0.05), and significantly lower in terms of symptoms(P < 0.05).CONCLUSION: The present study suggests that performing scar-producing moxibustion by heat-stimulating the acupoints Zusanli(ST 36) and Feishu(BL13) effectively decreases the NLR and improves the quality of life in patients with NSCLC.

Clinical observation of Yiqi Qingdu Prescription(益气清毒方)on the treatment of intermediate-stage and advanced non-small-cell lung cancer

OBJECTIVE:To observe the effects of the Yiqi Qingdu prescription(益气清毒方)on intermediate-stage and advanced non-small-cell lung cancer(NSCLC).METHODS:In total,300 patients with intermediate-stage or advanced NSCLC were randomly and equally divided into three groups using computer-generated random numbers as follows:Western medicine(WM),Chinese medicine(CM),and integrated Traditional Chinese and Western Medicine(IM).After 3 months of treatment,the overall response rate(ORR);disease control rate(DCR);symptom score(SS);Karnofsky performance status(KPS);adverse event score;counts of CD3^(+),CD4^(+),and CD8^(+)cells;CD4^(+)/CD8^(+)ratio;and carcinoembryonic antigen(CEA)level were compared among the groups.RESULTS:The ORRs were 30.36%,20.24%,and 7.87%in the IM,CM,and WM groups,respectively,whereas the DCRs were 85%,75%,and 73%,respectively.Compared to the CM group,the ORR was significantly higher in the WM and IM groups,whereas the DCR was significantly higher in the IM group(all P<0.05).SS was obviously higher in the WM group than in the other two groups(both P<0.01).KPS was significantly lower in the WM group after treatment(P=0.005).The mean number of adverse events was significantly lower in the CM(2.2±1.3)and IM(2.4±1.3)groups than in the WM group(4.6±1.7,both P<0.05).CD3^(+)cell counts were significantly decreased in the WM group(P=0.031).In the IM group,CD8^(+)cell counts were increased after treatment,whereas the CD4^(+)/CD8^(+)ratio was decreased(both P<0.01).Compared with the WM group,CD3^(+)(P=0.01),CD4^(+)(P=0.044),and CD8^(+)(P=0.009)cell counts were significantly higher in the IM group,whereas the CD4^(+)/CD8^(+)ratio was significantly lower(P=0.011).Relative to the CM group,CD8^(+)cell counts were significantly higher(P=0.001)and the CD4^(+)/CD8^(+)ratio was significant ly lower in the IM group(P=0.001).CEA levels were significantly increased in the CM group(P=0.023).CONCLUSION:The Yiqi Qingdu prescription can improve the outcomes of WM in patients with NSCLC.

RNA干扰沉默IGF-Ⅰ R表达对非小细胞肺癌细胞生物学特性及化疗敏感性的影响

目的:评价RNA干扰(RNA interference,RNAi)技术,对人肺癌A549细胞系中胰岛素样生长因子类受体(IGF-Ⅰ R)表达的阻断效应,和IGF-Ⅰ R基因沉默后细胞增殖、凋亡等生物学特性及肿瘤细胞对化疗药物敏感性的改变。方法:应用U6启动子,介导DNA模板转录生成短发夹样RNA(shRNA),并转染人肺癌A549细胞株,从而产生IGF-Ⅰ R特异性小干扰RNA(siRNA),经RT-PCR和Western blot检测IGF-Ⅰ R表达的改变;联合应用化疗药物顺铂(DDP),通过MTT法和流式细胞技术等,观察细胞生长、细胞周期、细胞凋亡及DDP半数致死量(IC50)的变化。结果:IGF-Ⅰ R表达水平明显下降(抑制率高达89.8%),肿瘤细胞增殖能力明显减弱,细胞滞留于G0期的比例上升;DDP对肿瘤细胞24h、48h、72h的IC50均明显减少,IGF-Ⅰ R siRNA1组DDP作用72h的IC50为0.92 mg/L,明显低于control-siRNA组的3.77mg/L,0.5mg/L DDP联合IGF-Ⅰ R siRNA1作用48h后,A549细胞的生长抑制率达32.1%,明显高于control-siRNA组的18.9%,细胞凋亡率从27.8%上升至44.2%。结论:运用RNAi技术能有效抑制A549细胞IGF-Ⅰ R的表达,使细胞增殖能力减弱,化疗敏感性增加。

葡萄糖转运蛋白在非小细胞肺癌中的表达及其临床意义

目的:探讨葡萄糖转运蛋白(Glucose transporter,Glut)的两种异构体Glut1、Glut3及缺氧诱导因子-1(Hypoxia inducible factor-1,HIF-1)的亚基HIF-1α,在非小细胞肺癌中的表达及临床意义。方法:选取34例手术切除非小细胞肺癌(包括癌组织和癌旁组织)和17例肺良性病变标本,用免疫组织化学法测定Glut1、Glut3及HIF-1α在肺组织中的表达;用RT-PCR半定量检测Glut1、Glut3及HIF-1α的mRNA表达;用Western Blot检测Glut1、Glut3及HIF-1α蛋白的表达,并测两者相关性。结果:Glut1、Glut3及HIF-1α在肺癌组织中mRNA相对含量为0.689±0.245、0.506±0.246、0.693±0.248,对应癌旁组织为0.338±0.157、0.482±0.238、0.351±0.184,Glut1和HIF-1α在肺癌组织中显著升高(P<0.001),而Glut3差别无显著性(P>0.05)。Glut1、Glut3、HIF-1α在癌组织中蛋白相对含量为0.582±0.247、0.551±0.251、0.525±0.246,癌旁组织为0.288±0.151、0.436±0.224、0.261±0.135,在肺良性病变中为0.291±0.142、0.402±0.206、0.271±0.176,Glut1和HIF-1α在癌组织中的表达均明显高于癌旁组织(P<0.001)和肺良性病变组织(P<0.001);而Glut3差别无显著性(P>0.05)。Glut1和HIF-1α在低分化组明显高于中高分化组(P<0.05),期明显高于和期(P<0.05),且HIF-1α的表达与Glut1明显相关(r=0.854,P<0.01)。结论:在非小细胞肺癌中,Glut1和HIF-1α存在高表达,其表达与细胞分化程度、TNM分期密切相关,且Glut1和HIF-1α具有相关性。