Targeted therapy for intractable cancer on the basis of molecular profiles: An open-label, phase II basket trial (Long March Pathway).

Purpose: We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated. Materials and methods: The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients. Results: In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33-27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33-9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%). Conclusion: The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.

Exploring the molecular targets and mechanisms of [10]-Gingerol for treating triple-negative breast cancer using bioinformatics approaches, molecular docking, and in vivo experiments.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive among breast cancer subtypes with the worst prognosis. Ginger is widely used in pharmaceuticals and as food. Its anticancer properties are known, but the mechanism is still unclear. [10]-Gingerol is one of the main phenolic compounds isolated from ginger. Studying the biological effects of [10]-Gingerol is of great significance to understand the efficacy of ginger. METHODS: In this study, the therapeutic effects of [10]-Gingerol on TNBC cells were studied using network pharmacology, molecular docking, and in vitro experiments, and the target and mechanism of action were explained. RESULTS: A total of 48 targets of ginger for the treatment of TNBC were found. These targets might interfere with the growth of TNBC by participating in many pathways, such as endocrine resistance, progesterone-mediated oocyte maturation, estrogen signaling pathway, and cellular senescence. Prognostic analyses indicated that the JUN, FASN, ADRB2, ADRA2A, and PGR were the hub genes, while molecular docking predicted the stable binding of ADRB2 protein with drug compounds. Additionally, [10]-Gingerol could induce apoptosis by regulating the caspase activation. CONCLUSIONS: [10]-Gingerol affects the growth of TNBC through multiple action targets and participating in multiple action pathways. ADRB2 and apoptosis pathways might be important target pathways for [10]-Gingerol in the treatment of TNBC.

Caveolin-1 is a prognostic marker and suppresses the proliferation of breast cancer.

BACKGROUND: To explore the role of caveolin-1 (Cav-1) in breast cancer (BC). METHODS: Cav-1 expression data were downloaded from the Tumor Immune Estimation Resource (TIMER) and Gene Expression Omnibus (GEO) databases. We compared the expression of Cav-1 in different tumor tissues and between BC tissues and normal tissues (NTs), as well as the differences between different clinical traits. Kaplan-Meier survival analysis and univariate and multivariate Cox regression analyses were used to determine whether Cav-1 serves as a prognostic factor. The correlations of Cav-1 expression with the immune microenvironment and infiltrating immune cells were also analyzed. Quantitative polymerase chain reaction (qPCR) was used to detect Cav-1 mRNA expression in the MCF-7, SKB-R3, MDB-MB-231, and SUM-159 cell lines. LV-Cav-1-RNAi was transfected into MCF-7 and MDB-MB-231 cells, and the MTT assay was used to detect cell proliferation. Subsequently, MDB-MB-231 cells carrying the Cav-1-RNAi gene were used to determine the effects of Cav-1 knockdown on tumor growth in vivo using a severe combined immunodeficiency (SCID) model. RESULTS: Cav-1 was enriched in most solid tumors, and its expression was lower in BC tissues than in NT. Cav-1 expression was shown to be related to patients' clinical outcomes. Cav-1 was expressed in the MCF-7, SKB-R3, MDB-MB-231, and SUM-159 cell lines. The MTT assay revealed that the proliferative ability of MDB-MB-231 and MCF-7 cells was accelerated. The tumor volume of SCID mice administered with LV-Cav-1-RNAi cells was increased. CONCLUSIONS: These results suggest that Cav-1 may serve as a suppressor in the development of BC.

Effect of acupuncture at Fengchi (GB 20) on the activity of myosin light chain kinase in the middle meningeal artery of migraine modeled rats.

OBJECTIVE: To study the effect of acupuncture at Fengchi (GB 20) on the activation of myosin light chain kinase (MLCK) in the middle meningeal artery of migraine modeled rats. METHODS: Forty-four clean grade healthy female Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, blank control group, Fengchi (GB 20) acupuncture group, and Fengchi (GB 20) prevention group. Neurogenic inflammation of these rats was induced by electrical stimulation. The γ-32P infiltration method was then used to detect MLCK activation in the middle meningeal artery, and immunocytochemistry was applied to detect the structural protein expression of MLCK. RESULTS: The miaraine model was successfully established in the rats. Compared with the control group, MLCK activation was significantly decreased in the blank control group (P < 0.01). CONCLUSION: The activation of MLCK in the middle meningeal artery was increased by acupuncture at Fengchi (GB 20), indicating its effectiveness in preventing and curing on acute migraine attacks.

Preparative isolation and purification of lignans from Justicia procumbens using high-speed counter-current chromatography in stepwise elution mode.

Lignans, which are recognized as main constituents in Justicia procumbens, have attracted considerable attention due to their pharmacological activities, including antitumor, anti-hepatitic, cytotoxic, anti-microbial, and anti-virus properties. Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to the isolation and purification of four lignans (justicidin B (1), justicidin A (2), 6'-hydroxyjusticidin C (3) and lignan J1 (4)) from J. procumbens using stepwise elution with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at (1.3:1:1.3:1, v/v) and (2.5:1:2.5:1, v/v). The preparative HSCCC separation was performed on 300 mg of crude sample yielding compounds 1 (19.7 mg), 2 (9.86 mg), 3 (11.26 mg), and 4 (2.54 mg) in a one-step separation, with purities over 95% as determined by HPLC. The structures of these compounds were identified by MS, 1H-NMR and 13C-NMR. This is the first report on the application of HSCCC to the efficient separation of lignans from J. procumbens.

Effects of Sanyinjiao (SP6) with electroacupuncture on labour pain in women during labour.

OBJECTIVE: To evaluate the effects of Sanyinjiao (SP6) with electroacupuncture on labour pain in women during the labour process. METHODS: A total of 350 women in labour from three centres were randomly divided into the electroacupuncture group (acupuncture group), the sham electroacupuncture group (sham group) and the control group. Women in labour in the electroacupuncture group received the electroacupuncture on the point Sanyinjiao (SP6). The analgesic effect was self-rated by women in labour, using visual analogue scale (VAS). The duration and paralysis time of uterine contraction, uterine contraction regularity, degree of cervical extension, presentation of foetal descent, the condition of intra-partum haemorrhage and postpartum haemorrhage, labour manner, lochia, involution of uterus, milk secretion, neonate Apgar Score and neonate body height and weight were also measured. All data were analysed with Statistical Package for Social Sciences (SPSS) 12.0. RESULTS: Labour pain scores from women in the acupuncture group were less than in the control group at needle retaining at 30min, 2 and 4h after needle withdrawal. Other evaluated indices did not show significant differences among the three groups. No adverse events were observed during the labour process. CONCLUSION: SP6 with electroacupuncture could be an effective way for decreasing labour pain.

[Clinical observation on the effect of electroacupuncture of Sanyinjiao (SP 6) on labor].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of Sanyinjiao (SP 6) on labor in parturients. METHODS: A total of 349 parturients were randomly divided into EA (n=117), sham-EA (n=117) and control (n=115) groups. The visual analog scale (VAS) was used to assess the pain intensity of puerperas with labor before and after acupuncture intervention. After excluding those puerperas with cesarean section, the time required for each stage of labor and the total duration of labor were observed in 286 cases of natural delivery women including 92 cases in the control group, 94 cases in the sham-EA group and 100 cases in the EA group. EA (2 Hz/100 Hz, 20 mA) was given to the puerperas for 30 min after the needle in a cannula was tapped into Sanyinjiao(SP 6) and when the dilatation of cervix was about 2-3 cm wide. For puerperas of sham-EA group, the operation was similar, but no real acupuncture needle and no real electric current were given. RESULTS: The VAS score for childbirth pain intensity was significantly lower in EA group than in control group (P < 0.05) and had no significant difference between sham-EA and control group (P > 0.05). The duration of the active phase of the first stage of labor was significantly lower in EA group than in sham-EA group (P < 0.05), but had no significant difference between sham-EA and control groups (P > 0.05). No significant differences were found among the 3 groups in the latency of the first stage of labor, in the duration of the 2nd and the 3rd stages of labor and in the total phase of labor (P > 0.05). CONCLUSION: EA of SP 6 can relieve the pain intensity of the labor and shorten the duration of the active period of first stage of labor in puerperas, suggesting an improvement of the quality of delivery after EA.

[Clinical application of acupuncture and moxibustion to the treatment of gouty arthritis and analysis on their therapeutic effects].

In the present paper, the authors make a summary on the clinical application of acu-moxibustion therapy in the treatment of gouty arthritis in recent 10 years. Acupuncture needles often used are filiform needle, red-hot needle, moxibustion-warmed needle and three-edged needle. Clinical studies have showed that acupuncture therapy has a definite efficacy in relieving gouty arthritis and has its clinical characteristics, such as faster efficacy, lower relapse rate, etc. in comparison with medication.