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.

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.

Aquaporin 5 Expression and Its Relationship to Apoptosis in Different Grades of Differentiated Non-Small Cell Lung Carcinoma

Aquaporin 5 has been recently found as an important oncogenic marker whose expression levels seem to be determined by the level of cellular differentiation. Despite aquaporin volume decrease (AVD) being the most conserved earliest event in apoptosis, there is still a paucity of studies exploring on aquaporin expression and its relationship with apoptosis in cancer. The aim of this study was to investigate the expression of aquaporin 5 channel protein and to explore on its relationship with apoptosis in well and poorly differentiated non-small cell lung carcinoma both in-vivo and in-vitro. Findings from the study showed that the expression of AQP5 both in-vivo and in-vitro was dependent on the type and degree of tumour differentiation. In-vivo, an increase in aquaporin 5 expression was associated with an increased apoptosis in both poorly and highly differentiated adenocarcinoma (AC) while there was no association between aquaporin 5 expression and apoptosis in both poorly and highly differentiated squamous cell carcinoma (SCC). In vitro, differentiation therapy in the form of ATRA decreased both cell proliferation and increased the expression of AQP5 in A549 cells. The cytomorphological changes, expression of differentiation markers and flow cytometry apoptotic results were dependent on the dose of ATRA treatment. In conclusion, a higher expression of aquaporin 5 was found to promote the rate of the apoptotic process in lung adenocarcinoma (AC).

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.

安罗替尼联合程序性死亡蛋白-l抑制剂治疗晚期非小细胞肺癌患者的临床疗效

【目的】探讨安罗替尼联合程序性死亡蛋白-l(programmed death-1,PD-1)抑制剂联合治疗晚期非小细胞肺癌(NSCLC)患者的疗效。【方法】回顾性分析90例NSCLC患者的临床资料,按照治疗方法不同分为对照组(n=30,采用安罗替尼治疗)和观察组(n=60,接受安罗替尼联合PD-1抑制剂治疗)。比较两组患者的近期疗效、生存情况和药物安全性。【结果】观察组治疗后客观缓解率(ORR)为11.67%(7/60),疾病控制率(DCR)为60.00%(36/60),分别高于对照组的6.67%(2/30)和33.33%(10/30),且差异有统计学意义(P<0.05)。观察组患者的中位无进展生存期(PFS)为10个月,中位总生存期(OS)为13个月,高于对照组患者(中位PFS为7个月,中位OS为11个月),且差异有统计学意义(P<0.05)。两组各项不良反应发生率比较,差异均无统计学意义(P>0.05)。【结论】安罗替尼联合PD-1抑制剂治疗晚期NSCLC患者,可有效提高患者的近期疗效,同时延长患者的生存期。

Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

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.

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.

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.

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.

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.

Clinical pathology of nodal micrometasteses in non-small cell lung cancer

Objective:To explore whether the conventional pathologic stages of some non-small cell lung cancer (NSCLC) patients were underestimated.Methods:195 lymph node samples were taken from 25 NSCLC patients during the operations.Firstly,each resulting tissue block was processed for routine paraffin embedding.Then the 6～10 serial sections were chosen,each 5 μm thick,from every paraffin block of the lymph node.Finally,the first and the second last sections of each lymph node were stained by hematoxylin eosin (HE),and the other serial sections were used for the immunohistochemical (IHC) staining examination with the monoclonal antibody against cyokeratin 19.Results:With HE staining,30 of the 195 regional lymph nodes revealed dominant nodal metastases,and none showed micrometastases.IHC staining was performed on 135 lymph nodes that were identified as free of metastases by HE staining,31 showed micrometastases;none showed gross nodal metastases.There was a significant difference between HE staining staging and IHC staining staging (P<0.05).Conclusion:Conventional HE staining can accurately detect gross nodal metastases in the lymph nodes of NSCLC patients,but is unfit for detecting lymph nodal micrometastases.IHC staining analysis can significantly facilitate the detection of occult micrometastatic tumor cells in lymph nodes,and its assessment of nodal micrometastases can provide a refinement of TNM stage for NSCLC patients.Our results provide a rationale for extensive lymph nodes sampling.

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.

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.

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.

Bcl-2相关抗凋亡基因3对非小细胞肺癌细胞增殖和迁移的影响

目的探讨Bcl-2相关抗凋亡基因3(BAG3)对非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞增殖和迁移能力的影响。方法通过查询并整理TCGA数据库,对不同肿瘤中的BAG 3表达进行泛癌分析。通过蛋白免疫印迹实验检测NSCLC细胞系(H1299、A549、H460、Anip973、PC9、H358和95-D细胞)以及人正常肺上皮细胞系Beas-2B中BAG3蛋白的相对表达量。H1299细胞分别转染Flag(A组)、Flag-BAG3质粒(B组),A549细胞分别转染siControl(C组)和siBAG3(D组)。通过蛋白免疫印迹实验检测质粒和小干扰RNA转染效率;采用CCK-8和平板克隆实验检测BAG3对NSCLC细胞增殖能力的影响;采用细胞划痕和Transwell实验检测BAG3对NSCLC细胞迁移能力的影响。结果BAG 3 mRNA在6种肿瘤中的表达均高于正常组织(t=8.45~24.13,P<0.05)。各NSCLC细胞系中BAG3的表达水平均明显高于Beas-2B细胞(t=5.76~15.34,P<0.05)。相比于A组,B组细胞中BAG3蛋白的表达水平显著升高(t=6.01,P<0.05);相比于C组,D组细胞中BAG3的蛋白水平明显降低(t=4.59,P<0.05);相比于A组,B组细胞增殖和迁移能力明显增强(t=5.12~17.10,P<0.05);相比于C组,D组细胞增殖和迁移能力明显下降(t=6.26~14.13,P<0.05)。结论BAG 3在NSCLC组织和细胞中高表达,并可促进NSCLC细胞的增殖和迁移。

动态监测血清血清鳞状上皮细胞癌抗原细胞角蛋白19血清片段21-1人附睾蛋白4水平在非小细胞肺癌患者疗程中的变化及其临床价值

目的动态监测血清鳞状上皮细胞癌抗原(SCC-Ag)、细胞角蛋白19血清片段21-1(CYFRA21-1)、人附睾蛋白4(HE4)水平在非小细胞肺癌患者疗程中的变化,并分析其临床应用价值。方法自2021年1月至2023年9月择取我院非小细胞肺癌患者108例为研究组,另收集同期良性肺病患者108例为作为对照组。分别检测良性肺病患者及非小细胞肺癌患者入院时血清SCC-Ag、CYFRA21-1、HE4水平;对比研究组不同治疗疗程患者血清各指标水平,并分析其诊断价值。结果入院时血清SCC-Ag、CYFRA21-1、HE4比较,研究组高于对照组(P<0.05);研究组患者血清SCC-Ag、CYFRA21-1、HE4水平:术后1 d>术后7 d>术后30 d>术后90 d;入院时血清SCC-Ag、CYFRA21-1、HE4水平联合诊断非小细胞肺癌的曲线下面积(AUC)为0.923,灵敏度为88.0%,特异度为83.3%。结论血清中SCC-Ag、CYFRA21-1、HE4表达水平在非小细胞肺癌患者中升高,并在不同术后疗程中存在降低,并发现三者联合检测可提高非小细胞肺癌的诊断效率,为肺癌的早期诊断及疗效评估提供新的手段。