DNA-PK inhibition synergizes with oncolytic virus M1 by inhibiting antiviral response and potentiating DNA damage.

Oncolytic virotherapy is a promising therapeutic strategy that uses replication-competent viruses to selectively destroy malignancies. However, the therapeutic effect of certain oncolytic viruses (OVs) varies among cancer patients. Thus, it is necessary to overcome resistance to OVs through rationally designed combination strategies. Here, through an anticancer drug screening, we show that DNA-dependent protein kinase (DNA-PK) inhibition sensitizes cancer cells to OV M1 and improves therapeutic effects in refractory cancer models in vivo and in patient tumour samples. Infection of M1 virus triggers the transcription of interferons (IFNs) and the activation of the antiviral response, which can be abolished by pretreatment of DNA-PK inhibitor (DNA-PKI), resulting in selectively enhanced replication of OV M1 within malignancies. Furthermore, DNA-PK inhibition promotes the DNA damage response induced by M1 virus, leading to increased tumour cell apoptosis. Together, our study identifies the combination of DNA-PKI and OV M1 as a potential treatment for cancers.

[Logistic regression analysis on therapeutic effect of acupuncture on neck pain caused by cervical spondylosis and factors influencing therapeutic effect].

OBJECTIVE: To explore the main factors influencing the therapeutic effect of acupuncture on neck pain caused by cervical spondylosis, so as to provide references for further increasing the therapeutic effect of acupuncture. METHODS: One hundred and six cases were randomly divided into an observation group and a control group, 53 cases in each group. The observation group was treated with routine acupuncture at Dazhui (GV 14), Jingbailao (Ex-HN 15) and Jianzhongshu (SI 15); and the control group was treated with sham acupuncture at 1 cm lateral to Bailao (Ex-HN 15) and Jianzhongshu (SI 15). The needles were retained for 20 min in the two groups and infrared radiation was used for adjuvant treatment in this period. Northwick Park Neck Pain Questionnaire (NPQ) was used to assess the patients' quality of life before and after the treatment. The potential influential factors were analyzed by Logistic regression. RESULTS: The effective rate was 75.5% in the observation group and 52.8% in the control group with a significant difference between the two groups (P<0.05). The Logistic regression analysis indicated that the therapeutic effect in the observation group was superior to the control group (OR = 2.670), and both the attack frequency and duration of the neck pain will influence the therapeutic effect (OR = 1.055 and OR = 2.446). CONCLUSION: Acupuncture has a better therapeutic effect on neck pain caused by cervical spondylosis, and patient's clinical history about attack frequency and duration of neck pain are factors influencing clinical therapeutic effect.

Analysis on the effect of acupuncture in treating cervical spondylosis with different syndrome types.

OBJECTIVE: To observe the clinical effect of acupuncture in treating cervical spondylosis with different syndrome types. METHODS: One hundred and seventeen patients were randomized into the treated group: (59 cases), treated with normal acupuncture, and the control group (58 cases), treated with sham acupuncture, operated once every other day, 9 times in total (in 18 days) as one therapeutic course, and a succeeding 3-month follow-up study was carried out after terminating the therapy. The efficacy of treatment was evaluated with the Northwick Park Neck Pain Questionnaire (NPQ) and Visual Analogue Scale (VAS), and the scores gained in patients with different syndrome types were analyzed with a general linear model. RESULTS: The NPQ and VAS: scores showed a linear decreasing tendency in both groups at the time of ending treatment and the 1st month of follow-up, but showed a secondary curve increasing tendency in the 3rd month of follow-up. Multivariate analysis showed the difference was of statistical significance (P<0.05). However, the analysis through lead-in of syndrome type as an individual influencing factor showed that syndrome type exerts a significant influence on VAS score (P<0.05), but has insignificant influence on the NPQ score (P>0.05). CONCLUSION: Acupuncture shows: good immediate effect in treating cervical spondylosis, but its long-term effect is not satisfactory. The difference in syndrome type may have some impact on the effects of acupuncture in alleviating pain, but exerts no evident influence on the comprehensive effect.