MicroRNAs modulation in lung cancer: exploring dual mechanisms and clinical prospects

The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably cancer.Within this context,miRNAs encapsulated in exosomes manifest a diversified impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these processes.This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer.Tumor-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness.Conversely,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective inhibitors.Distinct miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the specific miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.

Effect of etoposide plus thalidomide as maintenance therapy on progression-free survival of elderly patients with advanced non-small cell lung cancer

Objective The aim of the study was to evaluate the efficacy and safety of etoposide plus thalidomide as maintenance therapy for elderly patients with advanced non-small cell lung cancer（NSCLC） without disease progression after first-line chemotherapy.Methods After four to six cycles of platinum-based first-line therapy, 64 elderly patients with advanced NSCLC without disease progression who were treated in the General Hospital of Shenyang Military Region（China） from 2014 to 2016 were enrolled in this study. According to the different maintenance treatment methods, patients were divided as having received etoposide plus thalidomide therapy（treatment group, n = 32） and best supportive care（control group, n = 32）. Disease control and progression-free survival（PFS） were compared between the two groups. Results The recent curative effect objective response rates of the treatment group and the control group were 31.3% and 3.1%, respectively, and the disease control rates were 71.9% and 31.3%, respectively. The Kaplan-Meier survival curves of the two groups were significantly different（χ2 = 26.532, P = 0.001）. The median PFS for the treatment group and control group was 6.0 months [95% confidence interval（CI） = 4.3–7.9 months] and 3.2 months（95% CI = 2.6–3.8 months）, respectively. The side effects in the treatment group included hematologic abnormalities, gastrointestinal toxicity, and impaired liver function, which were relieved after symptomatic support therapy and drug withdrawal.Conclusion Etoposide plus thalidomide as maintenance therapy is associated with a significantly longer PFS with tolerable toxicity for elderly patients with advanced NSCLC.AcknowledgementThe authors would like to thank Liu Zhongzheng for his technical assistance.

Development of a new choroidal metastasis in resistance to crizotinib therapy in anaplastic lymphoma kinaserearranged non-small cell lung cancer

INTRODUCTION Non-small cell lung cancer（NSCLC）is a common malignant disease with an extremely poor prognosis.Lung cancer has been reported to metastasize to the eye in 0.2%to7%of patients based on clinical studies,and in 6%to 7%of patients based on postmortem histopathologic studies.

CLINICAL STUDY IN ACCELERATED HYPERFRACTIONATED IRRADIATION IN THE TREATMENT OF LOCAL ADVANCED NON-SMALL CELL LUNG CANCER

Objective To evaluate the effect of accelerated hyperfractionated irradiation (AHFJ) and conventional fractionated irradiation (CFI) for local advanced non- small cell lung cancer (NSCLC). Methods The patients of AI-IFJ group were irradiated to large-field target volume by a daily fraction of 2Gy, and small-field target volume by a daily fraction of 1Gy with more than 6h interval. The total dose of large-field target volume was SOGy/25Fx/SW and of small-field target volume was 7SGy/SOFx/5W. The patients in CFI group were irradiated by a daily fraction of 2Gy to the total dose of 66Gy/33Fx/6. 6W. After 3 months of radiotherapy, the tumor response rates of complete recovery (CR), partial recovery (PR), and no change (NC) and 1- and 2- year survival rate in the two groups were observed. Results The tumor response rates of CR,PR,NC in AHFI group and CFI group were 22.9%(8/35), 60.0%(21/35), 17.1%(6/35) and 11.4% (4/35), 51.4% (18/35), 37.2% (13/35) respectively (P>0. 05). All patients were followed up 2 years or more. The 1- and 2- year survival rates in AHFI group and CFI group were 62.9% (22/35), 31 .4% (11/35) and 42.9% (15/35) , 17.1% (6/35) respectively (P< 0.05). The incidences of esophagitis and pneumonitis in AHFI group and CFI group were 34.3% (12/35), 22. 9% (8/35) and 40.0% (14/35), 17.1% (6/35)(P>0. 05). Conclusion In comparison with CFI, AHFI may increase 1- and 2- year sur-vival rate after treatment of local advanced non-small cell lung cancer, while the radio-reactions, either early or late, did not increase significantly.

Adjuvant Effects of Fermented Red Ginseng Extract on Advanced Non-Small Cell Lung Cancer Patients Treated with Chemotherapy

Objective： To investigate the adjuvant therapeutic effects of fermented red ginseng（FRG） extract on non-small cell lung cancer（NSCLC） patients treated with chemotherapy. Methods： A total of 60 patients with advanced NSCLC were assigned to two groups using a random number table, i.e., the gemcitabine plus cisplatin（GP） chemotherapy alone group（26 patients） and the FRG ＋ GP chemotherapy group（34 patients）, for 60-day treatment. Patients were then assessed according to the Fatigue Symptom Inventory, Chinese medicine symptoms score, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Karnofsky Performance Status Scale, and Functional Assessment of Cancer Therapy-Lung. In addition, chemotherapy toxicity and tumor biomarkers were measured. Results： For NSCLC patients after chemotherapy, FRG extract significantly improved the FSI score, CM symptoms score, psychological status, physical conditions, and quality of life and reduced chemotherapy toxicity（P〈0.01）, but the expression levels of carcinoembryonic antigen, cytokeratin-19 fragments, and neuron-specific enolase were not significantly different between the chemotherapy alone and the FRG ＋ chemotherapy groups or between pre-and post-treatments（P〉0.05）. Conclusions： This study demonstrated that FRG extract had an adjuvant effect on advanced NSCLC patients treated with chemotherapy. Further studies with a larger sample size will verify the current findings.

Theraputic Effect on Carboplatin and Etoposide Combinative Therapy on 123 Lung Cancer Cases.

The clinical effcct of Carboplatin and Etoposide (CE regimen) on 58 cases of small cell lung cancer (SCLC) and 65

MULTIMODALITY THERAPY INCLUDING SURGICAL RESEC-TION FOR LIMITED SMALL CELL LUNG CANCER

From 1975 through 1990, 199 patients with limited small cell lung cancer (LSCLC) were subjected to multimodality treatment including surgical resection combined with chemotherapy or chemoradiotherapy in our department. The median postoperative survival time of the 199 patients was 39 months, and the 5-year survival rate was 26%, which was decreased with increase of tumor-stage. In comparison of the survival time of patients in Stage Ⅰ and those in Stage Ⅲa, there was a significant difference (P<0.01). There were no significant differences in survival rate of 3 and 5 years between the patients receiving chemotherapy prior to or after surgical resection. The improvement in survival was documented by surgical resection combined with chemotherapy or chemoradiotherapy for LSCLC. The effect of multimodality treatment is correlated with tumor P-TNM staging, the involvement of lymph node, especially that of the mediastinal lymph node, is a negative factor influencing the prognosis. Surgical resection as an initial management, followed by chemotherapy or chemoradiotherapy may be indicated in LSCLC patients of Stage Ⅰ, Stage Ⅱ and some Stage Ⅲa as the cancer can be resected completely.

Application of Response Evaluation Criteria of Traditional Chinese Medicine for Solid Tumor in Advanced Non-Small Cell Lung Cancer

Objective：To evaluate the objectivity and comprehensiveness of Response Evaluation Criteria of Traditional Chinese Medicine for Solid Tumor（Draft,REC-TCM-ST） in application of Chinese medicine therapeutic effect in patients with advanced non-small cell lung cancer（NSCLC）.Methods：A retrospective clinical research was used in 104 NSCLC patients in stages of Ⅲ-Ⅳ,53 cases were in Chinese medicine（CM） group and 51 cases were in Western medicine（WM） group.The therapeutic effect of the two groups was evaluated with both REC-TCM-ST and Response Evaluation Criteria in Solid Tumor（RECIST）.Kaplan-Meier method was used to analyze the survival time.Kappa test method was used to test the consistency of the two kinds of evaluation results.Results：According to REC-TCM-ST,the effective rate on relieving tumor mass in the CM group was significantly lower than that in the WM group（P〈0.05）,but there was no significant difference in tumor-mass stable rate（P〉0.05）;the symptom of weakness in the CM group was improved significantly,indicating better therapeutic effect than that in the WM group（P〈0.01）.Karnofsky score in the CM group was significantly better than that in the WM group（P〈0.01）.In terms of survival conditions,the median survival time and the survival rate of 6 months,1 year and 2 years of the CM group were higher than the WM group.The total effective rate was 9.62%,and the total stable rate was 72.12%for 104 cases according to RECIST;while the total effective rate was 34.62%,and the total stable rate was 84.62%according to REC-TCM-ST,thus there were significant differences between the results of the two criteria（P〈0.01）,and there was also some consistency between them,but not satisfactory.Conclusions：REC-TCM-ST was used to evaluate the therapeutic effect of CM in the treatment of advanced NSCLC,which shows that its evaluation results can better reflect the advantages and disadvantages of CM,and the effectiveness of CM is more objective and comprehensive than RECIST,so REC-TCM-ST is worthy of further improvement and clinical expansion.

Clinical benefit of gemcitabine plus cisplatin 3-week regimen for patients with advanced non-small cell lung cancer: a prospective observational study

Background Platinum-based chemotherapy has been proved effective in patients with advanced non-small cell lung cancer (NSCLC). This study evaluated the effectiveness and safety of first-line chemotherapy with gemcitabine plus cisplatin (GEM-Cis) 3-week regimen in routine care of Chinese patients with advanced NSCLC. Methods Two hundred and twenty-one patients with NSCLC stage IIIb or IV were enrolled and 209 were eligible for effectiveness and safety analysis. The median age was 58 (range 29 to 79) years. The percents of cases in stage Ⅳ and stage Ⅲb were 52.2% and 47.8%; of Karnofsky performance score (KPS) less than 80 and 80-100 were 37.3% and 62.7% and of adeno-cancer and non-adeno-cancer were 59.8% and 40.2%. The average number of completed chemotherapy cycles was three. Measures of effectiveness included clinical benefit, significant clinical response (SCR) and adverse effects of GEM-Cis in the treatment of NSCLC at stages Ⅲb/Ⅳ.Results KPS increased from 79±9 at baseline to 86±10 after chemotherapy (P<0.01). Lung cancer symptom scale (LCSS) score of pain, dyspnea and cough increased from 77±24, 74±22 and 63±19 to 92±15, 90±14 and 86± 15, respectively (P<0.01). The clinical benefit rate was 85.2% [95% confidence interval (CI) 80.3%-90.0%]. The SCR was 89.5% (95% CI 85.3%-93.7%). Median survival time was 7.8 months (95% CI 7.1 months-9.1 months). Sixty-four patients (30.6%) experienced an adverse effect that was deemed clinically significant. Only one patient (0.5%) was hospitalized due to chemotherapy related adverse effects. Life-threatening toxicity was observed in two patients (1.0%).Conclusion First-line chemotherapy with GEM-Cis in the routine care of Chinese patients with advanced NSCLC is effective and safe.

Anti-tumor effects of combined doxorubicin and siRNA for pulmonary delivery

Direct administration of drugs and genes to the lungs by pulmonary delivery offers a potential effective therapy for lung cancers.In this study,combined doxorubicin（DOX） and Bcl2 siRNA was employed for cancer therapy using polyethylenimine（PEI） as the carrier of Bcl2 siRNA.Most of the DOX and siRNA possessed high cellular uptake efficiency in B16F10 cells,which was proved by FCM and CLSM analysis.Real-time PCR showed that PEI/Bcl2 siRNA exhibited high gene silencing efficiency with 70%Bcl2 mRNA being knocked down.The combination of DOX and siRNA could enhance the cell proliferation inhibition and the cell apoptosis against B16F10 cells compared to free DOX or PEI/Bcl2 siRNA.Furthermore,the biodistribution of DOX and siRNA via pulmonary administration was studied in mice with B16F10 metastatic lung cancer.The results showed that most of the DOX and siRNA were accumulated in lungs and lasted at least for 3 days,which suggested that combined DOX and siRNA by pulmonary administration may have high anti-tumor effects for metastatic lung cancer treatment in vivo.