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.

Glabridin and Anti-Non-Muscle Myosin IIA Therapy Disrupts Non-Small Cell Lung Carcinoma Motility

Lung cancer is the leading cause of cancer related death in the United States killing over 130,000 people each year. While a combination of chemo and radiation therapy may be effective, surgery is still required for many patients. Without surgery, the disease may progress and lead to metastases. We sought to determine if treatment with anti-non-muscle myosin IIA antibody would inhibit movement of the cells in the presence and absence of glabridin (an isoflavonoid compound shown to inhibit cell migration by inhibiting myosin). We compared inhibition by glabridin to that of an anti-non-muscle myosin IIA antibody and a combination therapy of both at 12 and 24 hours post wound creation. Cells that took up the anti-non-muscle myosin IIA antibody were greatly inhibited in motility and exhibited no significant change in wound healing. Glabridin treatment resulted in a dramatic increase in wound size within 12 hours and regeneration within 24 hours. The greatest decrease in motility was observed in cells treated with the combination of both glabridin and anti-non-muscle myosin IIA antibody. By 24 hrs, cell migration had halted due to death of the cells resulting from this combination. Further testing needs to be done to determine a safe mode of delivery of the combination therapy to ensure only local distribution. Controlled release drug delivery depot systems have been used as a means to provide local release of drugs intra-tumorally or adjacent to the cancerous tissue after surgical resection and have great potential.

EGFR mutation identifies distant squamous cell carcinoma as metastasis from lung adenocarcinoma

Lung cancer metastasis is typically determined by histologic similarity between distant and primary lesions. Herein, we present a 70-year-old Japanese woman with an adenocarcinoma in her lung and a squamous cell carcinoma in her femur; both tumors had an identical epidermal growth factor receptor mutation, G719 S. This indicated that both tumors had a common origin, despite their histologic dissimilarity. The tumor in the femur was thus identified genetically as a lung cancer metastasis. This case suggests that genetic analysis can determine whether a distant lesion is a lung cancermetastasis, particularly when the histology differs from that of the primary lesion.

The ^(18)F-FDG uptake in non small cell lung carcinoma correlates with the DNA-grading of malignancy

In order to evaluate correlation of glucose metabolism and DNA ploidity of tumors, the uptake of 18F-Deoxyglucose (FDG) by PET prior to surgery and the DNA cotent and DNA-grading of malignancy (DNA-MG) of Schiff-stained nuclei obtained from fresh tumor fragments by means of image cytometry were studied, and thereafter the correlation between standardized uptake value (SUV) and (DNA-MG) was analysed in forty-nine patients with histologically proven non-small cell lung carcinoma (NSCLC). As a result of the DNA histograms of these 49 patients, 46 (93.88%) were aneuploid and only 3(6.12%) were tetraploid. A linear correlation of the SUV versus the (DNA-MG) (r=0.336, p=0.024) was found, demonstrating that 18F-FDG PET as a non-invasive metabolic imaging technique, may also provide inforrnation correlated to malignant DNA patterns which may be valuable in malignant differentiation and prognostic prediction.

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.

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.

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.

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.

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.

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.

LungPoint导航联合吲哚菁绿荧光成像在Ⅰa期非小细胞肺癌淋巴结采样中的应用价值

目的:寻找一种准确定位Ⅰa期非小细胞肺癌患者(NSCLC)前哨淋巴结(SLN)的方法,验证SLN作为淋巴结取样样本的合理性。方法:采用前瞻性研究方法,参照入组标准纳入2021年1月至2023年12月在山东省公共卫生临床中心胸外科临床分期为Ⅰa期NSCLC住院患者50例,术前借助LungPoint导航气管镜下肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像完成SLN定位,并对包括SLN在内的区域淋巴结行病理学检查,使用该方法对SLN的识别率、准确率与假阴性率等验证其作为淋巴结取样样本的合理性。结果:50例患者中,41例检测到SLN,识别率为82.0%(41/50),经病理检测发现3例共计9枚SLN有淋巴结转移(阳性),其中1例亦检出非前哨淋巴结(N-SLN)阳性2枚。9例患者未检测到SLN,清扫淋巴结54枚,未发现转移淋巴结,故SLN准确率为100.0%(41/41),假阴性率为0(0/3)。结论:借助LungPoint气管镜在肿瘤周围注射示踪剂吲哚菁绿,通过荧光胸腔镜成像探寻SLN技术具有较高的区域淋巴结转移预测性,有望成为指导Ⅰa期NSCLC系统性淋巴结采样的依据。

Analysis of prognostic factors for overall survival in patients with advanced non-small cell lung cancer treated with second line chemotherapy

Aim: The aim of this study was to investigate prognostic factors for survival in patients with advanced NSCLC who receiving second-line chemotherapy. Methods: We retrospectively reviewed data of 116 patients with NSCLC receiving second-line treatments from October 2010 to December 2012 in Clinic for Lung Diseases of Clinical center Nis, Department for Pulmonary Oncology. Thirteen potential prognostic factors were chosen for analysis. Univariate analysis was conducted to identify prognostic factors associated with progression free survival and overall survival. Multivariate analysis included the prognostic significance factors in univariate analysis. Results: The univariate analysis for progression free survival (PFS) and overall survival (OS) was identified to have prognostic significance: performance status, smoking, weight loss, comorbidity, number of meta localization, first-line chemotherapy regimen and response to first-line chemotherapy. Nevertheless, multivariate Cox prortional hazard regression analysis showed that performance status (PFS: p = 0.000, OS: p = 0.000) weight loss ≥ 5% (PFS: p = 0.000, OS: p = 0.002), comorbidity (PFS: p = 0.001, OS: p = 0.012) and four places of meta localization (PFS: p = 0.021, OS: p = 0.021) were considered independent prognostic factors for both, progression free survival and overall survival. Conclusion: Performance status, weight loss ≥ 5%, comorbidity and higher number of meta localization were identified as prognostic factors for survival in advanced NSCLC patients receiving second-line chemotherapy treatment. These findings may help pretreatment prediction of survival and may facilitate in the future integration new agents into second-line treatment.

CLINICAL EFFICACY OF VINORELBINE PLUS CISPLATIN IN ADVANCED NON-SMALL CELL LUNG CANCER

A clinical study of the efficacy of vinorelbine plus cisplatin regimen in the management of advanced NSCLC was performed in 35 patients. Five of the 35 patients failed to finish one cycle of chemotherapy with this regimen because of severe and intractable leukopenia or rapid progress of the disease. Tumor response and toxicity were evaluated in the remaining 30 cases. Results showed that, with this regimen, the objective response rate (CR+PR) was 46.7%. The most common toxicity was leukopenia; other side effects included alopecia, gastrointestinal reactions, slight and transient renal and hepatic impairment and peripheral neuropathy. It suggested that vinorelbine plus cisplatin is a safe and effective regimen in the management of advanced NSCLC.

ADJUVANT CHEMOTHERAPY FOLLOWING RADICAL SURGERYFOR NON-SMALL CELL LUNG CANCER:A RANDOMIZED STUDY

Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage I–III) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX) 300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 dl, cisplatin (DDP) 20 mg/m2, d1–5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600–900 mg/d for 1 year (adjuvant chemotherapy group). The other 35 patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4% in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage III was 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage I–II in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage III, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.

Risk factors of brain metastasis of lung squamous cell carcinoma:a retrospective analysis of 188 patients from single center

Background:To explore risk factors and the efficacy of treatment strategies for brain metastasis (BM) in squamous cell carcinoma (SCC) of the lung.Methods:The clinical data of 188 pathologically confirmed as squamous cell carcinoma or adenosquamous carcinoma patients were studied retrospectively. Factors including age (<60 vs.≥60), gender, stage at diagnosis, T status (T1-2 vs. T3-4), N status (N0-1 vs. N2-3), histology (squamous vs. adenosquamous), smoking history (non-smoker vs. currentsmoker) and serum tumor markers (normal vs. elevated) were analyzed.Results:The incidence of BM was 19.1％(36/188) in our cohort. Patients who were female (p=0.005), had advanced disease at diagnosis (p<0.001), had adenosquamous carcinoma histology (p=0.033) or had elevated serum level of CEA at diagnosis (p<0.001) had significantly higher incidence of BM. In multivariate analysis, female (p=0.034, HR=18.874) and elevated serum level of CEA at diagnosis (p=0.009, HR=19.824) were independent risk factors of BM. BM patients who received additional systemic therapy after local therapy had significantly longer post-BM survival than those who received local therapy only (p=0.004, HR=0.058). Gemcitabine/platinum-containingregimen (GP) and taxans/platinum-containing regimen (TP) led to comparable brain-metastasis-free survival (BMFS) (p=0.10).Conclusions:Females and patients with elevated serum level of CEA at diagnosis had a higher risk of developing BM. The following systemic therapy after local therapy prolonged the survival of BM patient, but the efficacy of GP and TP was comparable in terms of preventing BM.

基于脑MRI的机器学习预测非小细胞肺癌T790M突变

目的:本研究基于脑部T_(1)C和T_(2)W MRI建立人工智能模型,预测肺癌脑转移患者在靶向治疗中的耐药性T790M突变。方法:本研究收集80例肺癌脑转移患者(2017年6月—2019年12月)的T_(1)C和T_(2)W MRI影像和临床数据进行回顾性分析(患者按照2∶1的比例分成训练集和测试集)。采用无监督k-means算法将肿瘤区域划分为高亮度区域和低亮度区域,提取不同区域的影像组学图像特征构建模型,评估每个模型的诊断效果。绘制受试者工作特征(Receiver operating characteristic,ROC)曲线,计算ROC曲线下面积(Area under curve,AUC)、特异性和敏感性作为模型评价指标,分析模型的潜在临床应用价值。结果:对T_(1)C和T_(2)W MRI和临床特征融合的统计计算表明,本研究建立的模型对T790M突变具有良好的预测能力,在训练集和测试集上的AUC分别为0.899和0.818。结论:本研究建立的计算机模型可以有效预测肺癌脑转移患者T790M突变,具有潜在的临床辅助诊断价值。

EGFR突变NSCLC组织LncRNA TCF7L2表达及临床病理特征和预后分析

目的 探究长链非编码RNA(LncRNA)转录因子7类似物2(TCF7L2)在表皮生长因子受体基因(EGFR)突变的非小细胞肺癌(NSCLC)组织表达及其与病人临床病理特征和预后相关性。方法 选取2019年3月—2021年6月河北北方学院附属第一医院治疗的EGFR突变NSCLC病人104例为研究对象,分别取其癌组织和癌旁组织应用逆转录PCR(RT-PCR)检测LncRNA TCF7L2的表达,比较不同组织TCF7L2表达及其与临床病理特征和预后的相关性。结果 RT-PCR检测结果显示,癌组织中LncRNA TCF7L2表达量显著高于癌旁组织(t=12.410,P<0.05)。与LncRNA TCF7L2低表达病人比较,高表达者发生淋巴结转移更多、肿瘤体积更大(χ^(2)=4.579、7.762,P<0.05);LncRNA TCF7L2高表达病人6、9和12个月的生存率较低,但差异均无统计学意义(P>0.05)。结论 LncRNA TCF7L2在EGFR突变NSCLC病人癌组织表达高于癌旁组织,且TCF7L2高表达病人的淋巴结转移风险较高、肿瘤体积较大,其生存率可能较低。

YTH结构域家族蛋白2和叉头蛋白转录因子3在肺腺癌中的表达关系研究

目的 分析YTH结构域家族蛋白2(YTHDF2)及叉头蛋白转录因子3(FOXO3)在肺腺癌病人中的表达及与预后的关系。方法 收集2020年1月至2021年5月在郑州大学第一附属医院行手术治疗的肺腺癌病人癌组织及对应的癌旁组织(距离癌组织5 cm以上)80对,收集病人临床病理资料;利用癌症基因组图谱(TCGA)数据库查询YTHDF2、FOXO3基因在肺腺癌中的表达水平;采用免疫组织化学法检测YTHDF2、FOXO3蛋白在肺腺癌组织中的表达情况;分析YTHDF2、FOXO3蛋白水平与肺腺癌病人临床病理资料的关系;分析肺腺癌中YTHDF2与FOXO3基因表达水平的相关性;对病人进行为期3年的随访,分析病人3年累积生存率。结果 YTHDF2、FOXO3蛋白在肺腺癌组织中的高表达率分别为34.00%、26.00%,明显低于癌旁正常组织中79.48%、61.54%(P<0.05)。YTHDF2蛋白表达情况与肺腺癌病人年龄、淋巴结转移和分化程度相关(P<0.05);与TNM分期、性别无关(P>0.05);FOXO3蛋白表达情况与肺腺癌病人性别和分化程度相关(P<0.05);肺腺癌组织中YTHDF2蛋白高表达组和低表达组病人3年累积生存率分别为53.30%、14.00%,经log-rank比较,差异有统计学意义(P<0.05);FOXO3蛋白高表达组和低表达组病人3年累积生存率分别为64.50%、12.20%,经Log-Rank比较,差异有统计学意义(P<0.05)。结论 YTHDF2、FOXO3在肺腺癌组织中均低表达,与病人肿瘤分化程度及3年累积生存率有关,有望成为评估肺腺癌病人预后的生物标志物。

奥西替尼联合吉西他滨治疗伴肾转移的老年晚期NSCLC患者的临床疗效

【目的】探讨奥西替尼联合吉西他滨治疗伴肾转移的老年晚期非小细胞肺癌(NSCLC)患者的临床疗效。【方法】本院收治的238例老年晚期NSCLC患者,随机分为对照组和观察组,每组119例。对照组给予奥西替尼治疗,观察组在此基础上另给予顺铂、吉西他滨治疗。比较两组治疗3个疗程后的疗效及治疗前后肿瘤标志物、肾功能指标的变化,药物安全性和1年生存情况。【结果】观察组临床控制率高于对照组(P<0.05)。两组治疗后癌胚抗原(CEA)、胃泌素释放肽前体(ProGRP)、鳞状细胞癌抗原(SCCA)水平较治疗前均降低(P<0.05),且观察组CEA、ProGRP、SCCA均低于对照组(P<0.05)。两组治疗前后的血尿素氮、血肌酐水平比较,差异均无统计学意义(P>0.05)。两组不良反应发生率比较,差异无统计学意义(P>0.05)。观察组1年总存活曲线优于对照组(P<0.05)。【结论】奥西替尼联合吉西他滨方案治疗伴肾转移的老年晚期NSCLC患者疗效显著,可降低肿瘤标志物水平,延长患者近期生存时间,且安全性良好。