Ping-ping Li

Marsdenia tenacissima extract restored gefitinib sensitivity in resistant non-small cell lung cancer cells

Most non-small cell lung cancer (NSCLC) patients responding to gefitinib harbor activating mutations in the epidermal growth factor receptor (EGFR). However, the responsive cases eventually develop the resistance to gefitinib. Besides, K-ras mutations were identified as the primary resistance to gefitinib. We investigated whether Marsdenia tenacissima extract (MTE, trade name: Xiao-Ai-Ping injection) combined with gefitinib could overcome the resistance of NSCLC cells to gefitinib. NSCLC cell lines with different sensitivities to gefitinib were studied. Cell growth and apoptosis were evaluated by MTT assay and flow cytometry, respectively. The EGFR-related signaling molecule phosphorylation was assessed by Western blotting. We found that MTE inhibited cell growth in gefitinib-sensitive and -resistant cells. In gefitinib-resistant cells, the MTE→MTE+gefitinib (M→M+G) treatment was most potent over the concurrent administration of MTE and gefitinib (M+G) or gefitinib→gefitinib+MTE (G→G+M) treatment in cell growth inhibition and apoptosis induction. The M→M+G treatment significantly reduced the phosphorylation of EGFR downstream signaling molecules PI3K/Akt/mTOR and ERK, on which MTE and gefitinib alone had no obvious effects on the resistant cells. The M→M+G treatment attenuated c-Met phosphorylation in H460 and H1975 as well. Thus, we found that the M→M+G treatment improved the sensitivity of resistant NSCLC cells carrying T790M or K-ras mutations to gefitinib, suggesting that the M→M+G treatment may be a promising therapeutic strategy to overcome gefitinib resistance in NSCLC.

Progress of research in antitumor mechanisms with Chinese medicine

The anti-tumor effects of Chinese herbal medicines and their prescription preparations attracted more and more attention at home and abroad. Thus, it is becoming a hot research topic to exploit the anti-tumor mechanisms of Chinese medicine, and some of them have been partly clarified with the improved research ability to date. In brief, the Chinese herbal medicines possess unique advantages on the treatment of tumors through their multiple actions on multiple targets.

Longer overall survival in a patient with advanced non-small cell lung cancer treated with Chinese medicine and chemotherapy

Non-small cell lung cancer(NSCLC)is the leading cause of cancer death in the industrialized world.Despite significant prog ress in early stage of the disease,the overall su rvival rates for advanced disease remain low.Herein we present a case of NSCLC who was treated with Chinese medicine and chemotherapy with a longer overall survival. Case Presentation A 57-year-old,non-smoking women was seen in the surgical ward at the Beijing Cancer Hospital and Institute on May 12,2005,because of a pancreatic mass. The patient had undergone an abdominal computed tomography(CT)scan at Shunyi Renmin Hospital,

Protective effect of Renshen Yangrong Decoction (人参养荣汤) on bone marrow against radiation injury in mouse

ObjectiveTo explore the effect of Renshen Yangrong Decoction (人参养荣汤, RYD) in protecting bone marrow from radiation injury.MethodsOne hundred and eighty Kuming mice were subjected to the three tests for anti-radiation injury effect evaluation, i.e. the test of peripheral white blood cell (WBC) count, the test of bone marrow nucleated cell count, and the bone marrow micronucleus test, using 60 mice for each test. The mice in each test were divided into 6 groups: the blank control group, the model control group, the positive control group treated by Shiyiwei Shenqi Tablet (十一味参芪片, 1.0 g/kg), and three RYD groups treated with high (42.0 g/kg), moderate (21.0 g/kg), and low (10.5 g/kg) doses of crude drugs of RYD, with 10 mice in each group. The treatment was given by gastrogavage perfusion continuously for 7–14 days before mice received 60Co-γ ray radiation and continued until the end of the experiment. The body weights of the mice were monitored, the changes in peripheral WBC and bone marrow nucleated cells were counted, and the variation in bone marrow micronucleated cells was observed on the respective appointed days.ResultsA significant decrease in body weight, peripheral WBC count, and bone marrow nucleated cell count, as well as marked changes in bone marrow micronucleated cells were observed in the mice after radiation, indicating that the radiation injury model was successfully established. As compared with the model control group, the decrease in body weight, peripheral WBC count, and bone marrow nucleated cell count, as well as the increase in bone marrow micronucleus cell count in the high dosage RYD treated group were obviously inhibited or lessened (P<0.05 or P<0.01).ConclusionRYD showed obvious protective effect in mice with bone marrow injury induced by radiation.

Anti-fatigue effect of Renshen Yangrong decoction (人参养荣汤) in mice

ObjectiveTo explore the anti-fatigue effect of Renshen Yangrong Decoction (人参养荣汤, RYD): in mice.MethodsOne hundred Kunming mice were randomly divided into 5 groups with 20 mice in each: group. The negative control group was treated with distilled water, the positive control group was treated with Shiyiwei Shenqi Tablet (十一味参芪片, 1.0 g/kg), the high-, medium- and low-dose RYD groups were treated with 42.0, 21.0 and 10.5 g/kg of RYD daily, respectively, by gastric infusion. At the end of the 7-day treatment, loaded swimming time, organ wet weight and coefficient, serum glucose, urea nitrogen, and hepatic glycogen levels were determined. The outcomes were compared among groups.ResultsAs compared with the negative: control group, the loaded swimming time was significantly increased in the positive control group, specifically the medium- and high-dose RYD groups (P<0.01). In addition, the wet weights and coefficients of the spleen and thymus, and the serum glucose and hepatic glycogen contents were increased, whereas serum urea nitrogen level was significantly decreased in the positive control group and the high dose RYD group (P<0.05 or P<0.01).ConclusionRYD showed an anti-fatigue effect in mice.

Injectable Chinese herbal formula Kang'ai for nonsmall cell lung cancer: Trial sequential analysis of 2,259 participants from 31 randomized controlled trials.

OBJECTIVEnThe aim was to evaluate the efficacy and safety of Kang ai (KA) injection for patients with nonsmall cell lung cancer (NSCLC). Furthermore, to identify if more trials are needed before reliable conclusions could be drawn with regard to these outcomes.nnnMATERIALS AND METHODSnWe searched the Cochrane library, PubMed, EMBASE, VIP, CBMdisc, and CNKI in September 2012, and then an additional updated search was conducted in January 2013. Only relevant randomized controlled trials (RCTs) on KA injection plus first-line cisplatin-based chemotherapy in the treatment of NSCLC were identified. Trials data was reviewed and extracted by two reviewers independently. The quality of included studies was assessed according to a statement from Cochrane Handbook. RevMan 5 Software and Trial sequential analysis (TSA) software were applied for data analyses.nnnRESULTSnA total of 31 RCTs involving 2259 patients were included. The results of meta-analysis showed that compared with chemotherapy alone, the combination of KA injection plus chemotherapy had a statistically significant benefit in improving clinical response rate (relative risk [RR] =1.29, 95% confidence interval [CI]: 1.17-1.41, P < 0.00001), clinical benefit rate (RR = 1.19, 95% CI: 1.14-1.25, P < 0.00001) and quality of life (RR = 1.79, 95% CI: 1.63-1.98, P < 0.00001); hematological toxicity (white blood cell) (RR = 0.71, 95% CI: 0.66-0.76, P < 0.00001) and nonhematological toxicity (nausea and vomiting) (RR = 0.73, 95% CI: 0.65-0.83, P < 0.00001) were improved as well. TSA showed that all cumulative Z-score crossed their monitoring boundaries, demonstrating that no more trials are needed before reliable conclusions could be drawn.nnnCONCLUSIONnCurrent evidence presented that KA injection might improve the therapeutic effect when combined with chemotherapy. Moreover, no more trials are needed in future according to TSA. Nevertheless, additional randomized studies investigating KA injection are needed to be further evaluated.

Recent highlights of experimental research for inhibiting tumor growth by using Chinese medicine.

To give an overview of contemporary experimental research using Chinese medicine (CM) for the treatment of cancer. As an integral part of mainstream medicine in the People’s Republic of China, CM emphasizes improvements in holistic physical condition instead of merely killing tumor cells, which is consistent with the current medical model that advocates patient-oriented treatment. Great progress has been made in experimental research, and the principle aspects include anti-tumor angiogenesis, inducing apoptosis and differentiation, reversing multidrug resistance, and improving immune function. As a current hot topic in cancer research, tumor microenvironment (TME) highlights the mutual and interdependent interaction between tumor cells and their surrounding tissues, and the CM treatment concept bears a striking resemblance to it. To date, primary points of TME include extracellular matrix remodeling, inflfl ammation, hypoxia, and angiogenesis, but trials using CM with a focus on TME are rare. Despite considerable recent development, experimental research on CM for solving cancer issues appears insufficient. Greater efforts in this field are urgently needed.

Clinical study on long-term overall survival of advanced non-small-cell lung cancer patients treated with Chinese medicine and western medicine

ObjectiveTo investigate the prognostic influence on long-term overall survival (OS) from treatment with Chinese medicine (CM) and chemotherapy or targeted therapy in advanced non-small-cell lung cancer (NSCLC) patients.MethodsThe clinical data of 206 advanced NSCLC patients who were treated with CM and Western medicine in Beijing Cancer Hospital from April 1999 to July 2013 were retrospectively analyzed. Long-term survivors were defined as OS ⩾ 3 years after treatment with CM and chemotherapy. Twenty-eight patients had OS ⩾ 3 years, 178 had OS < 3 years, and all clinical data were statistically analyzed with the Cox model. Variables were gender, age, smoking status, performance status (PS) score, pathological type, clinical stage, first-line chemotherapy, targeted therapy, and use of CM. Univariate survival analysis was performed using the Kaplan-Meier method and log-rank sequential inspection. Multivariate survival analysis was used to analyze the meaningful factors of univariate survival analysis with the Cox model.ResultsThe survival rate of patients with OS ⩾ 3 years was 13.6% (28/206). Cox multivariate regression analysis showed that PS score, clinical stage, disease control rate to first-line chemotherapy, and use of CM were independent factors of longterm OS (all <0.05). However, gender, age, smoking, and use of epidermal growth factor receptor tyrosinekinase inhibitor were not significant (P>0.05).ConclusionPS score, clinical stage, disease control rate to firstline chemotherapy, and use of CM are probably independent prognostic factors for long-term OS in patients with advanced NSCLC.

Clinical benefits as endpoints in advanced non-small cell lung cancer treated with integrative medicine

Abstract“Living with cancer” and symptom control are the features and advantages of integrative medicine in advanced non-small cell lung cancer (NSCLC) treatment. However, with the current concept of response evaluation criteria by the WHO and RECIST, it is difficult to exhibit the above characteristics. Clinical benefit (CB) is designed as an endpoint recently widely understood and accepted in oncology clinical trials. With the review of its definition and development, we suggest CB to be used as an endpoint in advanced NSCLC treatment with integrative medicine. CB should encompass two connotations: one is improved quality of life and symptom control and the other is disease control rate (DCR), including complete response (CR), partial response (PR), and stable disease (SD). We need to design randomized controlled trials (RCT) to investigate the interrelationship of CB rate and survival to provide high-grade evidence proving that advanced lung cancer patients could really benefit from integrative medicine treatment.

Effects of anastrozole combined with Shuganjiangu decoction on osteoblast-like cell proliferation, differentiation and OPG/RANKL mRNA expression

ObjectiveTo investigate the effects of anastrozole combined with Shuganjiangu decoction on osteoblast-like cells.MethodsHuman osteoblast-like cells MG-63 were cultured and divided into four groups: control, anastrozole, Shuganjiangu decoction (SGJGD), and anastrozole combined with SGJGD. Cell proliferation was investigated by MTT assay. Alkaline phosphatase (ALP) and osteocalcin, the indicators of cell differentiation, were evaluated by p-nitrophenylphosphate method and radioimmunoassay, respectively. Gene expressions of ALP, osteocalcin, osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) were examined by real-time PCR.ResultsAs evidenced by MTT assay, cell proliferation of MG-63 was inhibited by anastrozole, but stimulated with treatment of SGJGD alone and combined with anastrozole (P<0.01). Compared with control group, ALP activity was increased by the treatment of SGJGD alone and combined with anastrozole (P<0.01). Also, osteocalcin secretion was enhanced with the treatment of SGJGD single and combination with anastrozole (P<0.05). In the real-time PCR assay, gene expressions of ALP and osteocalcin were significantly increased (P<0.01 for ALP, P<0.05 for osteocalcin) by the treatment of SGJGD and anastrozole combined with SGJGD, but the expression of RANKL was decreased (P<0.05). Moreover, anastrozole combined with SGJGD upregulated gene expression of OPG (P<0.01).ConclusionSGJGD may alleviate the injury effects of anastrozole on MG-63 cells through adjusting bone formation and resorption indicators.