A fixed inhaled nitrous oxide/oxygen mixture as an analgesic for adult cancer patients with breakthrough pain: study protocol for a randomized controlled trial.

BACKGROUND: The management of breakthrough pain in cancer patients is always a challenge for medical professions. Occurring in 80% of cancer patients with advanced disease, breakthrough pain significantly decreases both patient's and caregiver's quality of life. The aim of this study is to assess the analgesic efficacy of a fixed inhaled nitrous oxide/oxygen mixture for adult cancer patients with breakthrough pain. METHODS/DESIGN: This is a randomized, placebo-controlled, double-blind study; it will be conducted in the General Hospital of Ningxia Medical University. The target study subjects are at least 18 years old, and are hospitalized cancer patients who are receiving routine opioids to control cancer-related pain but still experience breakthrough pain. A total of 240 patients will be recruited and randomly allocated between three treatment groups (A, B, C) and a control group (group D) in a ratio of 3:1. All treatment groups (A, B, C) will receive standard pain treatment (oral immediate-release morphine) plus a pre-prepared nitrous oxide/oxygen mixture, and the control group (D) will receive the standard pain treatment plus oxygen. Patients, doctors, nurses, and data collectors are all blind to the experiment. Assessments will be taken before treatment (T0), at 5 min (T1) and 15 min (T2) during treatment, and at 5 min after treatment (T3). The primary endpoint measures will be the percentage of patients whose pain is relieved at T1, T2, and T3. Secondary outcome measures will include the safety of treatment, adverse events, and satisfaction from both health professionals and patients. DISCUSSION: This study aims to provide an effective and practical intervention for a fast breakthrough pain relief and to improve cancer patients' quality of life significantly. The Evidence-Based Medicine Working Group claim that a randomized, double-blind, placebo-controlled experimental intervention is the most appropriate design to demonstrate its efficacy, so this study could give a new approach to controlling breakthrough pain episodes. TRIAL REGISTRATION: ChiCTR-INC-16008075 . Registered on 8 March 2016.

Inhibition of mitotic Aurora kinase A by alisertib induces apoptosis and autophagy of human gastric cancer AGS and NCI-N78 cells.

Gastric cancer is one of the most common cancers and responds poorly to current chemotherapy. Alisertib (ALS) is a second-generation, orally bioavailable, highly selective small-molecule inhibitor of the serine/threonine protein kinase Aurora kinase A (AURKA). ALS has been shown to have potent anticancer effects in preclinical and clinical studies, but its role in gastric cancer treatment is unclear. This study aimed to investigate the cancer cell-killing effect of ALS on gastric cancer cell lines AGS and NCI-N78, with a focus on cell proliferation, cell-cycle distribution, apoptosis, and autophagy and the mechanism of action. The results showed that ALS exhibited potent growth-inhibitory, proapoptotic, and proautophagic effects on AGS and NCI-N78 cells. ALS concentration-dependently inhibited cell proliferation and induced cell-cycle arrest at G2/M phase in both cell lines, with a downregulation of cyclin-dependent kinase 1 and cyclin B1 expression but upregulation of p21 Waf1/Cip1, p27 Kip1, and p53 expression. ALS induced mitochondria-mediated apoptosis and autophagy in both AGS and NCI-N78 cells. ALS induced the expression of proapoptotic proteins but inhibited the expression of antiapoptotic proteins, with a significant increase in the release of cytochrome c and the activation of caspase 9 and caspase 3 in both cell lines. ALS induced inhibition of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and p38 mitogen-activated protein kinase (MAPK) signaling pathways while activating the 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling pathway as indicated by their altered phosphorylation, contributing to the proautophagic effects of ALS. SB202191 and wortmannin enhanced the autophagy-inducing effect of ALS in AGS and NCI-N78 cells. Notably, ALS treatment significantly decreased the ratio of phosphorylated AURKA over AURKA, which may contribute, at least in part, to the inducing effects of ALS on cell-cycle arrest and autophagy in AGS and NCI-N78 cells. Taken together, these results indicate that ALS exerts a potent inhibitory effect on cell proliferation but inducing effects on cell-cycle arrest, mitochondria-dependent apoptosis, and autophagy with the involvement of PI3K/Akt/mTOR, p38 MAPK, and AURKA-mediated signaling pathways in AGS and NCI-N78 cells.

[Comparison of biological behavior between triple-negative breast cancer and non-triple- negative breast cancer].

OBJECTIVE: To summarize the epidemiological and biological features of triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (non-TNBC) to provide reference for devising individualized therapy and making prognostic evaluation. METHODS: The 5-year follow-up data were collected from 231 patients with pathologically established diagnosis of breast cancer treated in the Affiliated Hospital of Ningxia Medical University and Yinchuan People's Hospital between Jan. 2002 and Dec. 2004. The epidemiological and clinicopathological characteristics as well as the recurrence, metastasis and 5-year survival were compared between TNBC group and non-TNBC group. RESULTS: TNBC accounted 17.3% of the total breast cancer cases enrolled in this study. The tumor size and rates of recurrence and metastasis (especially visceral metastasis) were significantly greater in TNBC group than in non-TNBC group (P<0.05). The TNBC patients showed significantly lower 3- and 5-year survival rates than the non-TNBC patients (P<0.05), and TNBC patients with positive lymph nodes in clinical stage II had also a lower 5-year survival (P<0.05). Cox regression model analysis identified the patients' age, primary tumor size, clinical stages and triple-negativity as the independent risk factors for breast cancer. CONCLUSION: Compared to non-TNBC patients, patients with TNBC have higher rates of local recurrence and invasion, visceral metastasis and poorer prognosis, and a lower rate of 5-year survival. The triple negativity represents an independent factor for prognosis evaluation of breast cancer.