[Analysis of prescription regularity of traditional Chinese medicine for colorectal cancer based on data mining].

The tumor prescriptions contained in Dictionary of Tumor Formulas, Compendium of Good Tumor Formulas, Chinese Pharmacopoeia, Ministry of Health Drug Standards for Chinese Medicine Formulas and National Compilation of Standards for Proprietary Chinese Medicines were selected and organized to construct a database for tumor prescriptions, and the data mining techniques were applied to investigate the prescription regularity of colorectal cancer prescriptions. The formula data were extracted after screening in strict accordance with the inclusion and exclusion criteria, and were then analyzed with Microsoft Excel 2010 for frequency statistics, Apriori block provided by SPSS Clementine 12.0 software for correlation rule analysis, and arules and arulesViz packages in R 4.0.2 software for correlation rule visualization. In addition, SPSS 18.0 software was used for cluster analysis and factor analysis, in which cluster analysis was performed by Ochiai algorithm with bicategorical variables in systematic clustering method and factor analysis was performed mainly with principal component analysis. A total of 285 prescriptions were included in the statistical analysis, and the frequency statistics showed that 43 herbs had been used more than 16 times. The association rules analysis showed that 26 high-frequency me-dicine pair rules were obtained, and the association rules for those dispelling evil spirits, strengthening the body, resolving stasis, dispelling dampness, etc. were visualized. In the cluster analysis, we generated a dendrogram from which 7 groups of traditional Chinese medicines with homogeneity were extracted. 10 common factors were obtained in the factor analysis. The types of herbal medicines involved in the colorectal cancer prescription included anti-cancer antidotes, strengthening and tonifying medicines, blood-regulating medicines, and expectorant medicines, corresponding to the treatment for eliminating evil spirits, strengthening, resolving stasis, and expectorating dampness. The prescriptions for anti-cancer detoxification were normally based on the pairs composed of Scutellaria barbata-Hedyotis diffusa and Sophora flavescens, Sargentodoxa cuneata, S. barbata, often combined with stasis relieving drug and dampness eliminating drug, reflecting the characteristics of treatment for both toxicity and stasis, dampness and toxicity simultaneously. The prescriptions for strengthening the righteousness and tonifying the deficiency were composed of Astragalus membranaceus and Atractylodes macrocephala mainly, exerting the effect of benefiting Qi, strengthening the spleen and drying dampness, tonifying kidney and essence, tonifying blood and invigorating blood. Meanwhile, anti-cancer detoxification medicines shall be reduced as much as possible. The compatibility of the medicines for the intestinal tract reflected the principle of using the right medicine for the right condition and eliminating evil spirits or strengthening the body, as appropriate.

Retinal dehydrogenase 5 (RHD5) attenuates metastasis via regulating HIPPO/YAP signaling pathway in Hepatocellular Carcinoma.

Retinal dehydrogenase 5 (RDH5) is an important enzyme in the visual cycle. Several studies have reported that the RDH family may play crucial roles in tumor prognosis. However, the role of RDH5 in tumor prognosis is still unclear. We examined the mRNA level of RDH5 by using q-PCR in hepatocellular carcinoma (HCC) and adjacent non-cancerous tissues. The proliferation rate of HCC cells was detected by MTS assay, and the invasive ability was examined by transwell and scratch wound assays. The YAP protein localization and expression were visualized by immunofluorescence in two different cell lines. CpG islands in the promoter region were predicted by using the methprimer database. Clinical characteristics of a patient cohort data came from The Cancer Genome Atlas database. RDH5 was significantly downregulated in hepatocellular carcinoma tissues, and low RDH5 expression was associated with metastasis and poor patient prognosis. Functional assays revealed that the RDH5 promoter is methylated in HCC cell lines. Moreover, overexpressing RDH5 can suppress metastasis by reversing the epithelial-mesenchymal transition (EMT) process, and RDH5 also inhibits cell proliferation in HCC cell lines. Furthermore, suppressing RDH5 can activate the Hippo/YAP signaling pathway and promote the nuclear translocation of YAP. Clinical data demonstrated that RDH5 is an independent prognostic factor in HCC. In our study, we provided the first evidence that RDH5 plays a crucial role in suppressing proliferation and metastasis, and the RDH5 promoter is methylated in hepatocellular carcinoma. And as an important regulator, RDH5 can suppress the Hippo/YAP signaling pathway. Taken together, it revealed that RDH5 might be a potential therapeutic target in HCC patients.

Rosmarinic acid reverses non-small cell lung cancer cisplatin resistance by activating the MAPK signaling pathway.

Cisplatin (DDP) is one of the first-line chemotherapeutic agents for non-small cell lung cancer (NSCLC). However, repeated use of cisplatin in clinical practice often induces chemoresistance. The aims of this study were to investigate whether rosmarinic acid (RA) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms. Our data demonstrated that RA significantly inhibited NSCLC cell proliferation and cell colony formation in a dose-dependent manner, induced G1 phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to DDP. Mechanistically, RA inhibited NSCLC cell growth, arrested cell cycle, and induced apoptosis by activating MAPK and inhibiting the expression of P-gp and MDR1, which correspondingly enhanced p21 and p53 expression. We observed that the growth of xenograft tumors derived from NSCLC cell lines in nude mice was significantly inhibited by combination therapy. We demonstrate that RA is a potentially effective MDR reversal agent for NSCLC, based on downregulation of MDR1 mRNA expression and P-gp. Together, these results emphasize the putative role of RA as a resistance reversal agent in NSCLC.

Weipiling ameliorates gastric precancerous lesions in Atp4a-/- mice.

BACKGROUND: Altered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4-17, 2014; Kim and Bae, Curr Opin Hematol 25:52-59, 2018). However, few studies have investigated the role of metabolism in the development of gastric precancerous lesions (GPLs). Weipiling (WPL), a traditional Chinese medicine formula for treatment of GPLs. In this study, we evaluated the amelioration of GPLs by WPL and investigated the possible role of WPL in regulating glucose metabolism. METHODS: Firstly, the major components of WPL are chemically characterized by HPLC analytical method. In this study, we chose the Atp4a-/- mouse model (Spicer etal., J Biol Chem 275:21555-21565, 2000) for GPL analysis. Different doses of WPL were administered orally to mice for 10 weeks. Next, the pathological changes of gastric mucosa were assessed by the H&E staining and AB-PAS staining. In addition, TUNEL staining was used to evaluate apoptosis, and we further used immunohistochemically labelled CDX2, MUC2, ki-67, PTEN, and p53 proteins to assess the characteristic changes of gastric mucosa in precancerous lesions. The levels of such transporters as HK-II, PKM2, ENO1, MPC1, and LDHA were determined by Western blot analysis. Finally, we assessed the expression of mTOR, HIF-1α, AMPK, Rheb, TSC1 and TSC2 protein in the gastric mucosa of Atp4a-/-mice. RESULTS: In this work, we evaluated the protective effect of WPL on gastric mucosa in mice with precancerous lesions. The aberrant apoptosis in gastric mucosa of gastric pre-cancerous lesions was controlled by WPL (P<0.05). Furthermore, WPL suppressed the expression of CDX2, MUC2, ki-67, PTEN and p53, as the levels of these proteins decreased significantly compared with the model group (P<0.05). In parallel, WPL significantly suppressed the expression of transporters, such as HK-II, PKM2, ENO1, MPC1 and LDHA (P<0.05). In addition, mTOR, HIF-1a, AMPK, Rheb, TSC1 and TSC2 protein levels in gastric mucosa of Atp4a-/- mice in the high- and low-dose WPL groups were significantly lower than those in the model group (P<0.05), while the expression of TSC1 and TSC2 protein was significantly higher (P<0.05). CONCLUSIONS: Conclusively, WPL could ameliorate GPLs in Atp4a-/- mice by inhibiting the expression of transporters and suppressing the aberrant activation of mTOR/HIF-1α.

Tanshinone IIA combined with cisplatin synergistically inhibits non-small-cell lung cancer in vitro and in vivo via down-regulating the phosphatidylinositol 3-kinase/Akt signalling pathway.

Cisplatin represents one of the first-line drugs used for non-small-cell lung cancer treatment. However, considerable side effects and the emergence of drug resistance are becoming critical limitations to its application. Combinatorial strategies may be able to extend the use of cisplatin. Both Tanshinone IIA and cisplatin inhibit non-small-cell lung cancer cell growth in a time- and dose-dependent manner. When Tanshinone IIA was combined with cisplatin at a ratio of 20:1, they were observed to exert a synergistic inhibitory effect on non-small-cell lung cancer cells. The combination treatment was shown to impair cell migration and invasion, arrest the cell cycle in the S phases, and induce apoptosis in A549 and PC9 cells in a synergistic manner. KEGG pathway analysis and molecular docking indicated that Tanshinone IIA might mainly influence the phosphatidylinositol 3-kinase-Akt signalling pathway. In all treated groups, the expression levels of Bax and cleaved Caspase-3 were up-regulated, whereas the expression levels of Bcl-2, Caspase-3, p-Akt, and p-PI3K proteins were down-regulated. Among these, the combination of Tan IIA and cisplatin exhibited the most significant difference. Tanshinone IIA may function as a novel option for combination therapy for non-small-cell lung cancer treatment.

A pilot randomized controlled trial of acupuncture at the Si Guan Xue for cancer pain.

BACKGROUND: Pain is a common symptom in cancer patients. Acupuncture is a suggested treatment for a wide range of clinical conditions, usually for its beneficial effects on pain control. Si guan xue (the four points) have been widely used in clinical practice, and has shown that it is highly effective, effective in obtaining qi, shows strong acupuncture stimulation, and is simple to manipulate and safe to use. Therefore, the aim of this study is to test the protocol and safety of acupuncture at the si guan xue in the management of cancer pain. METHODS: This is a single-blind, randomized controlled pilot trial. 42 patients with moderate to severe cancer pain were randomly assigned to three different arms with seven sessions of treatment; that is, treatment arm 1 (the si guan xue arm, n = 14), treatment arm 2 (the si guan xue plus commonly used acupoints arm, n = 14) and the control arm (the commonly used acupoints arm n = 14). Primary outcomes included acupuncture relieving cancer pain, and patients' subjective improvement as measured by the Patient Global Impression of Change (PGIC). Secondary outcomes included the scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Karnofsky's Performance Status (KPS). RESULTS: The analysis showed that the cancer pain reduction in treatment arm 2 was most prominent on day 5 when compared with the control arm (P<0.05). There was no difference in the scores of PGIC, EORTC QLQ-C30 or KPS among the three groups (P>0.05). Furthermore, no serious adverse events were observed. CONCLUSIONS: These results indicate that acupuncture at the si guan xue plus commonly used acupoints tends to be effective in reducing cancer pain. However, the sample size was small, and a future multi-centre study with a larger sample size is warranted. TRIAL REGISTRATION: ChiCTR-IOR-15007471 (Retroactively registered on 28 NOV 2015).

[Efficacy Observation of Modified Yiqi Chutan Recipe Treating Mid-late Stage NSCLC Patients by CT Perfusion].

OBJECTIVE: To observe the effect of Modified Yiqi Chutan Recipe (MYCR) on blood flow perfusion in treating mid-late stage non-small cell lung cancer (NSCLC) patients by using multislice CT perfusion (CTP) , and to assess the relationship between each CTP parameter and the prognosis as well. METHODS: Totally 87 mid-late stage NSCLC patients were randomly assigned to the treatment group (44 cases, Shenyi Capsule + MYCR +chemotherapy) and the control group (43 cases, chemotherapy alone) in the ratio of 1:1. And 21 days consisted of 1 therapeutic course, 4 courses in total. All of them underwent CTP of primary tumor and routine thoracic CT examination (plain CT and enhancement CT) 3 times (before therapy, after 2 and 4 cycles). CT findings were analyzed for tumor size and perfusion parameters [blood flow (BF), blood volume (BV), permeability surface (PS), mean transit time (MTT), and time to peak (TP) before and after treatment, and relationship between perfusion parameters and prognosis was also assessed. RESULTS: In 87 cases, 7 dropped out and 80 cases were available, 40 in the treatment group and 40 in the control group. (1) The relief rate was 47.5% (19/40) and the total stable rate was 77.5% (31/40) in the treatment group, and they were 40.0% (16/40) and 65.0% (26/40) in the control group, with no statistical difference between the two groups (χ² = 0.672, 1.227; P > 0.05). (2) Compared with before treatment group in the same group, BF and PS decreased, and MTT increased in the two groups after 2 and 4 courses (P < 0.05); BE and PS decreased, and MTT increased in the control group after 2 courses (P < 0.05). Compared with the control group after 4 courses, BE decreased more significantly in the treatment group (P < 0.05). (3) After 4 courses, all patients were assigned to the remission group (35 cases) and the non-remission group (45 cases) according to the RECIST standard. Compared with before treatment in the same group, BF, BF, and PS all decreased, and MTT increased in the remission group after treatment (all P < 0.05); BF increased in the non-remission group after treatment (P < 0.05). (4) All patients were assigned to the BE increase group (34 cases) and the BE decrease group (46 cases) according to changed BE values after treatment. Results showed the mean survival rate was 246 days in the BF increase group (the 1-year accumulative survival rate being 13.0%) and 387 days in the BE decrease group (the 1-year accumulative survival rate being 53.1%). The life span was prolonged and the 1-year accumulative survival rate was elevated in the BE increase group, with statistical difference as compared with the BE decrease group (χ² = 19.057, P < 0.01). CONCLUSIONS: Shenyi Capsule plus MYCR could reduce BE in mid-late stage NSCLC patients , improve vascular permeability, showing better synergistic effect with chemotherapy. CTP could not only reflect the change of tumor size, but also reflect vascular function of the tumor. Meanwhile, changes of CTP parameters were closely associated with prognosis. Patients with post-treatment decreased BE value had better prognosis and longer life span.

[TCM Combined Western Medicine Treatment of Advanced NSCLC: a Preliminary Study of mIRNA Expression Profiles].

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 (P < 0. 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 (P<0.05). 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 (P <0. 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.

[Correlation analysis of efficacy of yiqi chutan recipe in treating NSCLC and P4HB expression].

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: P4HB might be taken as a factor for predicting the effect of YCR in treating NSCLC.

Sunitinib malate as first-line treatment for an advanced, poorly differentiated pancreatic neuroendocrine tumor.

Pancreatic neuroendocrine tumors (PNETs) are rare, accounting for approximately 2% of primary malignant tumors of the pancreas. Compared with common pancreatic ductal adenocarcinomas, they grow more slowly, are less invasive and have a better prognosis. At present, surgery is the preferred method of treatment of PNETs, and offers the only chance of a cure. However, owing to the occult onset of PNETs, once diagnosed they are often inoperable when the diagnosis is established, and the optimal treatment of patients with inoperable liver metastases remains uncertain. In recent years, targeted drug therapies have emerged and have proved effective in prolonging progression-free survival in patients with advanced well-differentiated PNETs, but hardly any progress has been made in the treatment of poorly differentiated PNETs. In the patient described in this report, who had a poorly differentiated PNET with multiple hepatic metastases and had refused cytotoxic chemotherapy, oral sunitinib malate treatment for 22 months with regular follow-ups proved tolerable and effective in significantly reducing the size of the intrahepatic masses.

Reduction in gefitinib resistance mediated by Yi-Fei San-Jie pill in non-small cell lung cancer through regulation of tyrosine metabolism, cell cycle, and the MET/EGFR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The Chinese herbal prescription Yi-Fei San-Jie pill (YFSJ) has been used for adjuvant treatment in patients with lung cancer for a long time. AIM OF THE STUDY: Reports have indicated that the combination of gefitinib (Gef) with YFSJ inhibits the proliferation of EGFR-TKI-resistant cell lines by enhancing cellular apoptosis and autophagy in non-small cell lung cancer (NSCLC). However, the molecular mechanisms underlying the effect of YFSJ on EGFR-TKI resistance and related metabolic pathways remain to be explored. MATERIALS AND METHODS: In our report, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), metabolomics, network pharmacology, bioinformatics, and biological analysis methods were used to investigate the mechanism. RESULTS: The UPLC-MS/MS data identified 42 active compounds of YFSJ extracts. YFSJ extracts can enhance the antitumor efficacy of Gef without hepatic and renal toxicity in vivo. The analysis of the metabolomics pathway enrichment revealed that YFSJ mainly affected the tyrosine metabolism pathway in rat models. Moreover, YFSJ has been shown to reverse Gef resistance and improve the effects of Gef on the cellular viability, migration capacity, and cell cycle arrest of NSCLC cell lines with EGFR mutations. The results of network pharmacology and molecular docking analyses revealed that tyrosine metabolism-related active compounds of YFSJ affect EGFR-TKIs resistance in NSCLC by targeting cell cycle and the MET/EGFR signaling pathway; these findings were validated by western blotting and immunohistochemistry. CONCLUSIONS: YFSJ inhibits NSCLC by inducing cell cycle arrest in the G1/S phase to suppress tumor growth, cell viability, and cell migration through synergistic effects with Gef via the tyrosine metabolic pathway and the EGFR/MET signaling pathway. To summarize, the findings of the current study indicate that YFSJ is a prospective complementary treatment for Gef-resistant NSCLC.

Current Advances and Outlook in Gastric Cancer Chemoresistance: A Review.

BACKGROUND: Surgical resection of the lesion is the standard primary treatment of gastric cancer. Unfortunately, most patients are already in the advanced stage of the disease when they are diagnosed with gastric cancer. Alternative therapies, such as radiation therapy and chemotherapy, can achieve only very limited benefits. The emergence of cancer drug resistance has always been the major obstacle to the cure of tumors. The main goal of modern cancer pharmacology is to determine the underlying mechanism of anticancer drugs. OBJECTIVES: Here, we mainly review the latest research results related to the mechanism of chemotherapy resistance in gastric cancer, the application of natural products in overcoming the chemotherapy resistance of gastric cancer, and the new strategies currently being developed to treat tumors based on immunotherapy and gene therapy. CONCLUSION: The emergence of cancer drug resistance is the main obstacle in achieving alleviation and final cure for gastric cancer. Mixed therapies are considered to be a possible way to overcome chemoresistance. Natural products are the main resource for discovering new drugs specific for treating chemoresistance, and further research is needed to clarify the mechanism of natural product activity in patients.

Mechanism of N-Methyl-N-Nitroso-Urea-Induced Gastric Precancerous Lesions in Mice.

Early diagnosis and treatment of gastric precancerous lesions (GPL) are key factors for reducing the incidence and morbidity of gastric cancer. The study is aimed at examining GPL in mice induced by N-methyl-N-nitroso-urea (MNU) and to illustrate the underlying mechanisms of tumorigenesis. In this study, we utilized an in vivo MNU-induced GPL mouse model, and histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (H&E-stain) and alcian blue (AB-PAS-stain). The level of miR-194-5p in the gastric mucosa was determined by real-time polymerase chain reaction. We used transmission electron microscopy to observe the effects of MNU on gastric chief cells and parietal cells. We performed immunohistochemical detection of HIF-1α, vWF, Ki-67, and P53, while the changes in the protein expression of key genes in LKB1-AMPK and AKT-FoxO3 signaling pathways were detected by western blot analysis. We demonstrated that the miR-194-5p expression was upregulated under hypoxia in GPL gastric tissues, and that a high miR-194-5p expression level closely related with tumorigenesis. Mechanistically, miR-194-5p exerted the acceleration of activities related to metabolic reprogramming through LKB1-AMPK and AKT-FoxO3 pathways. Furthermore, similar to miR-194-5p, high expression levels of AMPK and AKT were also related to the metabolic reprogramming of GPL. Moreover, we revealed the correlation between the expression levels of miR-194-5p, p-AMPKα, p-AKT, and FoxO3a. These findings suggest that miR-194-5p/FoxO3 pathway is important for the reversal of metabolic reprogramming in GPL. Thus, exploring strategies to regulate the miR-194-5p/FoxO3a pathway may provide an efficient strategy for the prevention and treatment of GPL.

Comprehensive analysis of somatic mutator-derived and immune infiltrates related lncRNA signatures of genome instability reveals potential prognostic biomarkers involved in non-small cell lung cancer.

Background: The function and features of long non-coding RNAs (lncRNAs) are already attracting attention and extensive research on their role as biomarkers of prediction in lung cancer. However, the signatures that are both related to genomic instability (GI) and tumor immune microenvironment (TIME) have not yet been fully explored in previous studies of non-small cell lung cancer (NSCLC). Method: The clinical characteristics, RNA expression profiles, and somatic mutation information of patients in this study came from The Cancer Genome Atlas (TCGA) database. Cox proportional hazards regression analysis was performed to construct genomic instability-related lncRNA signature (GIrLncSig). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the potential functions of lncRNAs. CIBERSORT was used to calculate the proportion of immune cells in NSCLC. Result: Eleven genomic instability-related lncRNAs in NSCLC were identified, then we established a prognostic model with the GIrLncSig ground on the 11 lncRNAs. Through the computed GIrLncSig risk score, patients were divided into high-risk and low-risk groups. By plotting ROC curves, we found that patients in the low-risk group in the test set and TCGA set had longer overall survival than those in the high-risk group, thus validating the survival predictive power of GIrLncSig. By stratified analysis, there was still a significant difference in overall survival between high and low risk groups of patients after adjusting for other clinical characteristics, suggesting the prognostic significance of GIrLncSig is independent. In addition, combining GIrLncSig with TP53 could better predict clinical outcomes. Besides, the immune microenvironment differed significantly between the high-risk and the low-risk groups, patients with low risk scores tend to have upregulation of immune checkpoints and chemokines. Finally, we found that high-risk scores were associated with increased sensitivity to chemotherapy. Conclusion: we provided a new perspective on lncRNAs related to GI and TIME and revealed the worth of them in immune infiltration and immunotherapeutic response. Besides, we found that the expression of AC027288.1 is associated with PD-1 expression, which may be a potential prognostic marker in immune checkpoint inhibitor response to improve the prediction of clinical survival in NSCLC patients.

Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages.

The purification, renewal and differentiation of native cardiac progenitors would form a mechanistic underpinning for unravelling steps for cardiac cell lineage formation, and their links to forms of congenital and adult cardiac diseases. Until now there has been little evidence for native cardiac precursor cells in the postnatal heart. Herein, we report the identification of isl1+ cardiac progenitors in postnatal rat, mouse and human myocardium. A cardiac mesenchymal feeder layer allows renewal of the isolated progenitor cells with maintenance of their capability to adopt a fully differentiated cardiomyocyte phenotype. Tamoxifen-inducible Cre/lox technology enables selective marking of this progenitor cell population including its progeny, at a defined time, and purification to relative homogeneity. Co-culture studies with neonatal myocytes indicate that isl1+ cells represent authentic, endogenous cardiac progenitors (cardioblasts) that display highly efficient conversion to a mature cardiac phenotype with stable expression of myocytic markers (25%) in the absence of cell fusion, intact Ca2+-cycling, and the generation of action potentials. The discovery of native cardioblasts represents a genetically based system to identify steps in cardiac cell lineage formation and maturation in development and disease.

[Consensuses on lung cancer treatment by Chinese medicine experts from Beijing and Guangzhou and medication features in the North and South China].

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.

[Effects of yiqi chutan recipe on tumor growth, survival time and expressions of PRDX-1 and PRDX-6 in Lewis lung carcinoma model mice with pi-deficiency syndrome].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (P < 0.05 or P < 0.01). 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 (P < 0.05). CONCLUSIONS: 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.

Ginsenoside Rg3 Promotes Cell Growth Through Activation of mTORC1.

Ginsenoside Rg3 is a steroidal saponin isolated from Panax ginseng. Previous studies have shown that Rg3 treatment downregulates the activity of rapamycin complex 1 (mTORC1) activity and inhibits the growth of cancer cells. However, the inhibitory effect of Rg3 on cancer cells is associated with high concentrations of Rg3 that are difficult to achieve in vivo. The human cervix adenocarcinoma HeLa cells were treated with Rg3. The protein levels of AMP-activated protein kinase alpha (AMPKα), protein kinase B(Akt), ribosomal S6 protein(S6), and Erk were determined by immunoblotting analyses. We used a fluorescent probe to detect reactive oxygen species (ROS) production in living cells. The oxygen consumption rate (OCR) was examined by the Seahorse Extracellular Flux Analyzer. The content of adenosine triphosphate (ATP) was measured by ATPlite kit and Mitotracker was applied to detect the mitochondria. We showed that at lower concentrations, Rg3 activates mTORC1 independent of AKT and AMP-activated protein kinase (AMPK). Rg3 promotes mitochondrial biogenesis and function, increases the oxygen consumption of mitochondria and the content of ATP. This effect is in contrast to that of high concentrations of Rg3, which inhibits cell growth. These findings demonstrate a pro-growth activity of Rg3 that acts through mTORC1 and mitochondrial biogenesis and suggest a dose-dependent effect of Rg3 on tumor cell growth.

Usage of Chinese Herbs in Cancer Patients in Southern China: A Survey.

OBJECTIVE: To study the use of Chinese medicine (CM) in cancer patients in southern China. METHODS: A total of 1,950 cancer patients finished questionnaires in four provinces in southern China. The survey included socio-demographic and clinical characteristics of participants, dosage forms, efficacy, and side effects. RESULTS: The study results showed that cancer patients with higher education (>12 years) were more likely to accept the treatment of Chinese herbs. There were 54.61% (1,065 cases) of patients chose Chinese herbs for the initial treatment and 14.46% (282 cases) chose Chinese herbs as monotherapy. Most patients (54.51%, 1,063 cases) continuously used CM for more than 6 months, and a few of them (212 cases) used CM for up to 3 years. All kinds of dosage forms of CM had been used, including CM decoction, CM patent prescription and CM injection. Concerning the efficacy in the view of patients, 40.31% (786 cases) believed that it would be effective to take Chinese herbs before they starting the anti-cancer treatment, and the percentage increased to 81.08% after 1-month CM treatment. The effect of Chinese herbs was mainly demonstrated by symptom relief and improvement of quality of life, and 8.31% (162 cases) of patients experienced control of tumor growth and decreased tumor markers. Furthermore, only 14.31% (279 cases) participants reported that they experienced side effects during CM treatment. CONCLUSION: This large scale investigation reflects the current situation of domestic CM usage objectively and comprehensively, which might provide new ways for cancer treatment.

Comprehensive analysis of an immune infiltrate-related competitive endogenous RNA network reveals potential prognostic biomarkers for non-small cell lung cancer.

Globally, non-small cell lung cancer (NSCLC) is the most common malignancy and its prognosis remains poor because of the lack of reliable early diagnostic biomarkers. The competitive endogenous RNA (ceRNA) network plays an important role in the tumorigenesis and prognosis of NSCLC. Tumor immune microenvironment (TIME) is valuable for predicting the response to immunotherapy and determining the prognosis of NSCLC patients. To understand the TIME-related ceRNA network, the RNA profiling datasets from the Genotype-Tissue Expression and The Cancer Genome Atlas databases were analyzed to identify the mRNAs, microRNAs, and lncRNAs associated with the differentially expressed genes. Weighted gene co-expression network analysis revealed that the brown module of mRNAs and the turquoise module of lncRNAs were the most important. Interactions among microRNAs, lncRNAs, and mRNAs were prognosticated using miRcode, miRDB, TargetScan, miRTarBase, and starBase databases. A prognostic model consisting of 13 mRNAs was established using univariate and multivariate Cox regression analyses and validated by the receiver operating characteristic (ROC) curve. The 22 immune infiltrating cell types were analyzed using the CIBERSORT algorithm, and results showed that the high-risk score of this model was related to poor prognosis and an immunosuppressive TIME. A lncRNA-miRNA-mRNA ceRNA network that included 69 differentially expressed lncRNAs (DElncRNAs) was constructed based on the five mRNAs obtained from the prognostic model. ROC survival analysis further showed that the seven DElncRNAs had a substantial prognostic value for the overall survival (OS) in NSCLC patients; the area under the curve was 0.65. In addition, the high-risk group showed drug resistance to several chemotherapeutic and targeted drugs including cisplatin, paclitaxel, docetaxel, gemcitabine, and gefitinib. The differential expression of five mRNAs and seven lncRNAs in the ceRNA network was supported by the results of the HPA database and RT-qPCR analyses. This comprehensive analysis of a ceRNA network identified a set of biomarkers for prognosis and TIME prediction in NSCLC.