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To evaluate the association between Chinese medicine (CM) therapy and disease-free survival (DFS) outcomes in postoperative patients with non-small cell lung cancer (NSCLC). This multiple-center prospective cohort study was conducted in 13 medical centers in China. Patients with stage I, II, or IIIA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network (NCCN) guidelines were recruited. The recruited patients were divided into a CM treatment group and a control group according to their wishes. Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression. Patients in the control group received CM therapy for less than 1 month. Follow-up was conducted over 3 years. The primary outcome was DFS, with recurrence/metastasis rates as a secondary outcome. Between May 2013 and August 2016, 503 patients were enrolled into the cohort; 266 were classified in the CM treatment group and 237 in the control group. Adjusting for covariates, high exposure to CM was associated with better DFS [hazard ratio (HR) = 0.417, 95% confidential interval (CI): 0.307–0.567)]. A longer duration of CM therapy (6–12 months, 12–18 months, >24 months) was associated with lower recurrence and metastasis rates (HR = 0.225, 0.119 and 0.083, respectively). In a subgroup exploratory analysis, CM therapy was also a protective factor of cancer recurrence and metastasis in both stage I–IIIA (HR=0.50, 95% CI: 0.37–0.67) and stage IIIA NSCLC postoperative patients (HR = 0.48, 95% CI: 0.33–0.71), DFS was even longer among CM treatment group patients. Longer duration of CM therapy could be considered a protective factor of cancer recurrence and metastasis. CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. (Registration No. ChiCTR-OOC-14005398)

Background Limited treatment strategies are available for squamous-cell lung cancer (SQLC) patients. Few studies have addressed whether immune-related genes (IRGs) or the tumor immune microenvironment can predict the prognosis for SQLC patients. Our study aimed to construct a signature predict prognosis for SQLC patients based on IRGs. Methods We constructed and validated a signature from SQLC patients in The Cancer Genome Atlas (TCGA) using bioinformatics analysis. The underlying mechanisms of the signature were also explored with immune cells and mutation profiles. Results A total of 464 eligible SQLC patients from TCGA dataset were enrolled and were randomly divided into the training cohort (n = 232) and the testing cohort (n = 232). Eight differentially expressed IRGs were identified and applied to construct the immune signature in the training cohort. The signature showed a significant difference in overall survival (OS) between low-risk and high-risk cohorts (P < 0.001), with an area under the curve of 0.76. The predictive capability was verified with the testing and total cohorts. Multivariate analysis revealed that the 8-IRG signature served as an independent prognostic factor for OS in SQLC patients. Naive B cells, resting memory CD4 T cells, follicular helper T cells, and M2 macrophages were found to significantly associate with OS. There was no statistical difference in terms of tumor mutational burden between the high-risk and low-risk cohorts. Conclusion Our study constructed and validated an 8-IRG signature prognostic model that predicts clinical outcomes for SQLC patients. However, this signature model needs further validation with a larger number of patients.

To observe the influence of fire needle stimulation at Sihua acupoints combined with chemotherapy on Th1/Th2 imbalance and performance status in the patients with advanced non-small cell lung cancer (NSCLC) so as to investigate its immunological mechanism underlying the improvement of lung cancer.Sixty eligible NSCLC inpatients were randomly assigned to a control group and a treatment group (Compared with the results before treatment, the levels of IL-2 and IFN-γ concentration increased obviously and the levels of IL-4 and IL-10 concentration as well as KPS score decreased significantly in the treatment group and the control group after treatment (allFire needle stimulation at Sihua acupoints improves the function of Th1 cells, and reduces the function of Th2 cells. As a result, the balance between Th1 and Th2 has been modified and the deterioration degree of the performance status been alleviated in the patients after chemotherapy.

Gefitinib is one of commonly used first-line treatment options for patients with positive EGFR mutation in non-small cell lung cancer (NSCLC). However, most patients with gefitinib treatment relapse over time due to the loss of drug sensitivity. Compound Kushen injection (CKI) has been used to treat lung cancer, including EGFR-mutated NSCLC. In this report, we examined the anti-cancer and drug sensitivity increased activities of CKI in gefitinib less sensitive NSCLC cell lines H1650 and H1975. Bioinformatics analysis was applied to uncover gene regulation and molecular mechanisms of CKI. Our results indicated that when associating with gefitinib in a dose-dependent fashion, CKI demonstrated the ability to inhibit the proliferation and to increase the sensitivity to gefitinib treatment in gefitinib less sensitive cell lines. This could be the results of down regulation of the PI3K/Akt/mTOR pathway and up regulation of autophagy, which were identified as the potential primary targets of CKI to increase gefitinib treatment effect.

Objective To preliminarily observe miRNA gene profiles in benefit serum of advanced non-small cell lung cancer (NSCLC) treated by TCM combined Western medicine (WM) , and to seek for molecular markers for its efficacy monitoring and prediction. Methods Recruited were 5 advanced NSCLC patients who received TCM combined WM treatment and obtained efficacy benefit ( as the treatment group) , 3 advanced NSCLC patients who received early treatment ( as the lung cancer group) , and 3 healthy subjects (as the control group). Serum samples were collected and total RNA was extracted using Trizol method. Using microRNA PCR ARRAY chip technology (product of Exiqon Company) , differentially miRNA expression profiling in serum between the lung cancer group and the control group, and between the treatment group and the lung cancer group were detected. Benefit miRNA expression profiling was ob- tained based on cluster analysis and comparative analysis. Results After tested by miRNA PCR ARRAY and managed by data analysis, a total of 42 miRNAs with more than 2 folds difference were screened in the lung cancer group and the control group, including 29 up-regulated and 12 down-regulated miRNAs. Be- sides, miR-10b-5p, miR-21-5p, miR-182-5p, miR-361-3p, and miR-382-5p were statistically different (P0. 05). A total of 45 miRNAs with more than 2 folds difference were screened in the treatment group and the lung cancer group, including 12 up-regulated and 33 down-regulated miRNAs. Fifteen miRNAs were statistically different including miR-137-3p, miR-182-5p, miR-376a-3p, miR-382-5p, miR-409-3p, miR-10a-5p, miR-21-5p, miR-29a-3p, miR-141-3p, miR-150-5p, miR-200c-3p, miR-342-3p, miR-365a-3p, miR-375, miR- 502-3p (P0.05). Totally 22 miRNAs were screened in the treatment group with more than 2 folds differ- ence as compared with the lung cancer group and with less than or equivalent to 2 folds difference as com- pared with the control group, including 7 up-regulated and 15 down-regulated miRNAs, of which, miR-127- 3p, miR-182-5p, miR-382-5p, miR-409-3p, miR-10a-5p, miR-21-5p, miR-141-3p, miR-342-3p were statistically different (P0. 05). Conclusion miRNAs including miR-21-5p, miR-182-5p, miR-382-5p are promising to become molecular markers for efficacy monitoring and prediction of advanced NSCLC treated by TCM combined WM, which provides reference for individualized treating advanced NSCLC.

Lung cancer is the leading cause of cancer death worldwide. Chemotherapy is one of the most effective strategies for lung cancer treatment. However, the side effects of chemotherapy limit the application of chemotherapeutic agents. The β-Asarone, a low-toxicity natural compound from a traditional Chinese medicinal herb, has been demonstrated to display anticancer activities in multiple cancer types. However, the anticancer activities of β-Asarone in lung cancer have not been shown, and the underlying molecular mechanisms are still unclear. In the current study, we show that β-Asarone displays a dose-dependent inhibitory effect on the viability of lung cancer cells. Additionally, β-Asarone significantly suppresses the cell migration, invasion, and adhesion of lung cancer cells. Moreover, β-Asarone induces apoptosis associated with the activation of caspase-9 and caspase-3, the upregulation of XAF1, Puma, Bax (Ser184) and Bad (Ser112), the downregulation of XIAP, Bcl-2 and Survivin, the translocation of Bax, Bad, phospho-Bax (Ser184), phospho-Bad (Ser112) and cytochrome C and the reduction of the mitochondrial membrane potential. Mechanistically, our study shows that β-Asarone inhibits Wnt/β-catenin signaling. Rescuing the activation of Wnt/β-catenin signaling overcomes β-Asarone-induced anticancer effects. Taken together, our data provide the first evidence of the anticancer effects of β-Asarone in lung cancer, demonstrates that the inhibition of Wnt/β-catenin signaling could be critical for β-Asarone-induced anticancer effects. Our study thus suggests a potential application of β-Asarone as an anticancer agent in the clinical treatment of lung cancer.

To study the predicting effect of proly 4-hydroxylase beta polypeptide (P4HB) in treating non-small cell lung cancer (NSCLC) patients by Yiqi Chutan Recipe (YCR).Totally 46 stage III and IV NSCLC patients were treated by YCR for 4 therapeutic courses. Effect was assessed by RECIST of solid tumor. P4HB expression was detected in the lung cancer tissue by immunohistochemical assay. Factors affecting disease control rates (DCR) of YCR were analyzed by Logistic regression analysis. The correlation between P4HB expression and the effect of YCR was analyzed.The DCR of advanced NSCLC treated by YCR was 36.96% (17/46 cases). P4HB was high expressed in advanced lung cancer tissue (6/15 cases). Gender, initial treatment, and retreatment are independent factors for affecting DCR of treating lung cancer by YCR.P4HB might be taken as a factor for predicting the effect of YCR in treating NSCLC.

To observe the effect of direct moxibustion at Sihua points on immune function and life quality of chemotherapy patients with non-small cell lung cancer.Eighty cases were randomly divided into a chemotherapy and moxibustion group (group A) and a chemotherapy group (group B), 40 cases in each one. Navelbine and cisplatin were applied in both groups. In addition, direct moxibustion at Sihua points which included Geshu (BL 17) and Danshu (BL 19) was used in the group A. Three moxa-cones were given on each acupoint, once a day, ten days treatment made one session and totally one session was required. The change of colony stimulating factor (CSF), tumor necrosis factor (TNF), interleukin-2 (IL- 2) and Karnofsky scale was compared between the two groups before and after treatment.After the treatment, the levels of serum CSF, IL-2 in the group A were higher than those in the group B (both P0.01), while the level of TNF in the group A was lower than that in the group B (P0. 01). Although Karnofsky score was decreased in the two groups (both P0.01), the score in the group A was higher than that in the group B (P0.01).Direct moxibustion at Sihua points could increase the levels of CSF and IL-2 and reduce TNF in the chemotherapy patients with lung cancer, which could improve immune function, clinical efficacy and life quality.

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).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.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 (P0.05), but there was no significant difference in tumor-mass stable rate (P0.05); the symptom of weakness in the CM group was improved significantly, indicating better therapeutic effect than that in the WM group (P0.01). Karnofsky score in the CM group was significantly better than that in the WM group (P0.01). 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 (P0.01), and there was also some consistency between them, but not satisfactory.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.

To study the consensuses on lung cancer treatment by Chinese medicine experts from North China and South China, and to analyze their medication features from viewpoints such as the medication frequency, combination laws, medication classification by collecting 800 recipes on the treatment of lung cancer patients prescribed by 8 Chinese oncologists from Guanganmen Hospital of China Academy of Chinese Medical Sciences, the Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, and Guangdong Provincial Hospital of Traditional Chinese Medicine. Results showed that coix seed, poria, pinelliae tuber were the three herbs most commonly used in treatment of lung cancer by all experts. They generally accepted Pi invigorating and phlegm removing method as the basic treatment method for treating lung cancer. Secondly, they usually used white peony root, heterophylla falsestarwort root, and ophiopogonis tuber, etc. (with higher medication frequency) to nourish yin and moisten Fei. Thirdly, consistency was also shown in clearing heat, detoxication, and anticancer. Smilacis glabra, Rhizoma Smilacis Glabrae, Herba Hedyotis diffusae, Herba Scutellariae Barbatae were herbs used by all experts. However, there were differences between oncologists in North China and South China. Oncologists in South China paid more attention to heat toxin and blood stasis, while those in North China paid more attention to supplementing both qi and yin.

To investigate the role of prolyl 4-hydroxylase beta polypeptide (P4HB) expressed in lung carcinoma and the intervention effect of Yiqi Chutan Formula (, YQCTF).Lung carcinoma model was established by subcutaneously inoculating LEWIS lung carcinoma cells in C57BL/6J mice. The differential expression of P4HB protein between the YQCTF (3.0 g/kg, gavage, once daily, 21 days) group and the control group was acquired by a 2 fluorescence difference gel electrophoresis (2D-DIGE), verified by Western blotting and identified by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS). The expression of P4HB and P4HB mRNA in cultured A549 cells from cisplatin (DDP) 1.5 µg/mL group and 15% serum combined with DDP 1.5 µg/mL group were detected by cellular immunohistochemistry and reverse transcription-polymerase chain reaction, respectively.The proteomics research discovered that one-third of differential proteins including P4HB were decreased in the YQCTF group (P0.01). Clinical pathology and tissue microarray studies showed that P4HB expression in lung cancer tissue was stronger than adjacent tissues and normal lung epithelial (P0.01). In the YQCTF and DDP combined groups, the expression of P4HB and P4HB mRNA in A549 cell were decreased significantly (P0.01).YQCTF could inhibit the LEWIS lung carcinoma's growth, decrease the expression of P4HB in LEWIS lung carcinoma and A549 cells. YQCTF might take effect through regulating P4HB in endoplasmic reticulum to inhibit the incidence and growth process of lung carcinoma.

To investigate the effects of Yiqi Chutan Recipe (YCR, a Chinese herbal prescription for invigorating qi and removing phlegm) on the growth and metastasis of tumor, survival time, and the expressions of peroxiredoxin (PRDX-1 and PRDX-6) in tumor tissue of C57BL/6J mice bearing Lewis lung carcinoma.Lewis lung carcinoma cells were transplanted to 90 C57BL/6J mice receiving preconditioning for inducing Pi-deficiency syndrome and divided into three groups treated respectively with saline, high dose YCR (3.0 g/kg) and low dose YCR (1.0 g/kg) once a day via gastric infusion. Besides, a group of 30 healthy mice simply received tumor cell transplantation was set up for controls. Ten mice selected from each group were sacrificed 21 days later, the size, weight and lung metastasis foci of tumor in mice were measured, and expressions of PRDX-1 and PRDX-6 in tumor tissue were detected using immunohistochemical method. The survival time of the remained 20 mice in each groups was observed.Tumor size, weight and the numbers of lung metastatic foci were (1.14 +/- 0.30) cm3, (0.83 +/- 0.26) g, (6.20 +/- 2.53) foci in the high dose YCR treated group, which were significantly lower than those in the control group [(2.83 +/- 0.35) cm3, (2.08 +/- 0.28) g, and (8.60 +/- 1.84) foci] respectively, also lower than those in the saline treated group [(2.29 +/- 0.49) cm3, (1.67 +/- 0.33) g and (8.70 +/- 2.00) foci]. The median survival time in the three groups, in above order, were 29.00 +/- 0.89 days, 22.00 +/- 0.75 days and 21.00 +/- 0.53 days; the average survival time in them 29.60 +/- 0.53 days, 22.90 +/- 0.50 days and 20.95 +/- 0.44 days; the PRDX-1 expression were 0.15 +/- 0.03, 0.52 +/- 0.07 and 0.61 +/- 0.09; and the PRDX-6 expression were 0.12 +/- 0.02, 0.43 +/- 0.06 and 0.56 +/- 0.07, all showed significant difference in comparing the indices in the high dose treated group with those in the control group and in the saline treated group (P0.05 or P0.01). The tumor growth inhibition rate was 50.30% in the high dose YCR group with life prolongation rate of 41.29%, all better than those in the low dose YCR treated group (P0.05).YCR can remarkably inhibit the growth and metastasis of Lewis lung carcinoma in mice with Pi-asthenia syndrome, prolong their survival period, and its mechanism is possibly related to the reduction of over expressed PRDX-1 and PRDX-6.

To study the apoptosis inducing effects of Hechanpian (HCP) on human lung adenocarcinoma A549 cells.HCP containing rat serum was prepared and applied on A549 cells. The cell growth inhibition rate was tested by MTT assay; the effect of HCP on cell apoptosis was observed with Propidium iodide (PI) staining and flow cytometry analysis; the mRNA expression of epidermal growth factor receptor (EGFR) was detected through RT-PCR.The growth of A549 cells was obviously inhibited after being treated by HCP containing serum, and the cells presented an apoptotic change. The cell apoptosis rate after treated by serum containing 10% and 20% HCP was 20.5% and 33.2%, respectively, significantly higher than that in the control (6.1% in cells didn't treated with HCP, P0.05). Compared with control, EGFR mRNA expression in HCP treated cells was significantly lower (P0.05).HCP has apoptosis inducing effect on A549 cell, and its molecular mechanism is probably correlated with the inhibition of EGFR gene transcription.

Senile lung cancer has its own characteristics, thus its treatment is also particular. Viewing from the therapeutic angle of integrative medicine, the current status of research and application of various clinical treatment strategies and measures for senile lung cancer were preliminarily reviewed in this paper in items of surgical operation, chemotherapy, radiotherapy, molecular target drugs therapy and Chinese medical therapy.

To observe the effect of traditional Chinese medicine (TCM) in improving quality of life of patients with non-small cell lung cancer (NSCLC) in III or IV stage, for establishing TCM therapeutic regimen on late NSCLC.A total of 294 patients in 6 hospitals were randomly assigned into three groups, 99 in the TCM group treated with TCM according to disease and syndrome differentiation, 92 treated with chemotherapy in the western group and 103 treated with combined therapy of TCM and chemotherapy in the integrative group. Six items, including physical status, social/family status, intercourse with physicians, emotional status, functional status and additional concerning status, were investigated and analyzed by using Functional Assessment of Cancer Therapy-lung (FACT-L).The scores of social/family status and intercourse with physicians were insignificantly different in all three groups before and after treatment (P0.05). The improvement of physical status in the TCM group, and that of emotional status, functional status and additional concerned status in the integrative medicine group were superior to those in the other groups (P0.05).TCM has certain antagonistic effect on the adverse reaction of chemotherapy, and it can improve the quality of life of patients to certain extent.

To observe the short-term therapeutic efficacy of integrated traditional and Western medicine (ITWM) in treating non-small cell lung cancer (NSCLC) in III and IV phase.Adopting the prospective, multi-centered, randomized and controlled method for clinical research, 324 patients who conformed to the enrolling standard were divided by ratio of 1:1:1 into the Chinese medicine (CM) group (n= 99), the ITWM group (n 03) and the Western medicine (WM) (n=92) group. The excluded or dropping off cases were 10 in CM, 6 in ITWM and 14 in WM. Clinical trials were conducted in 6 hospitals and 3 months of treatment was taken as one therapeutic course. The main observation indexes were tumor size, Karnofsky scores, body weight, adverse reaction, etc.The total effective rate of tumor remission in the 3 groups was 4.0%, 26.2%, and 14.1%, respectively, statistical significance was shown in the difference among them (chi = 21.72, P = 0.0000.017). The total tumor stabilization rate was 66.7 , 81.6%, and 76.1 , respectively, by rectification test, no significance was shown in difference among them (chi2 = 6.052, P = 0.0490.017). Karnofsky scoring showed that after 90 days of treatment, Karnofsky score raised in the CM and ITWM group, but lowered in the WM group, paired t-test showed significant difference in the ITWM group before and after treatment. The Karnofsky score in IWTM was higher than that in CM and WM with significant difference (H = 10.572, P = 0.0000.05). The patients' body weight in the 3 groups were all reduced. The reduction in the CM and ITWM group was lower than that in WM group, among which, significant difference was shown in CM and WM group when compared with the same group before treatment (P0.05). The effect in the ITWM and CM group was better than that in WM group in aspects of improving such tumor related symptoms as cough, short breath, anorexia, fatigue, etc. Observation of adverse reaction showed that lesser hemotoxicity of III and IV grade appeared in the CM and ITWM group than that in the WM group, and significant difference was shown in counts of white blood cells, granulocytes, platelets hemoglobin, etc. among the 3 groups (P0.01).ITWM therapy showed better short-term efficacy in treating patients with NSCLC than CM or WM alone, showing the superiority of ITWM therapy. It can be adopted as an effective therapeutic program with low-toxicity.

Chemotherapy is a treatment for stage III-IV non-small cell lung cancer (NSCLC), but the efficacy is not ideal. Traditional Chinese medicine (TCM) has certain effect on NSCLC. This study was to investigate various factors that affect the prognosis of advanced NSCLC, and evaluate the role of TCM in enlonging survival time of patients with stage III-IV NSCLC.The NSCLC patients who meet the inclusive criteria were randomized into TCM group, combination (TCM plus NP regimen) group, and chemotherapy group, and received relevant treatments. The median survival time (MST) was calculated by Kaplan-Meier method. The prognosis of the patients was analyzed by COX regression method.A total of 294 stage III-IV NSCLC patients were enrolled, of which 99 were in TCM group, 103 in combination group, 92 in chemotherapy group. The MST were 292 days in TCM group, 355 days in combination group, and 236 days in chemotherapy group; the cumulative survival rates were 45.38%, 48.86%, and 42.17%, respectively (P0.05). Cox regression analysis indicated that therapy, gender, disease course, erythrocyte sedimentation, KPS score, tumor size, and patient's weight were independent prognostic factors of stage III-IV NSCLC.Compare with chemotherapy alone, TCM combined with chemotherapy may prolong the survival time of stage III-IV NSCLC patients.