Morphine stimulates angiogenesis through Akt/mTOR/eIF4E activation under serum deprivation or H2 O2 -induced oxidative stress condition.

Morphine is an opioid analgesic drug routinely used to treat pain in several medical conditions including cancer. Increasing evidence has shown that morphine can directly modulate cancer growth via regulating angiogenesis. In this work, we investigated the effect of morphine on angiogenesis under pathological conditions. We showed that morphine, in a concentration typical of that observed in patient's blood, stimulates tumour angiogenesis under serum deprivation and H2 O2 -induced oxidative stress conditions. We found that morphine protected human lung tumour associated-endothelial cell (HLT-EC) against serum deprivation or H2 O2 -induced inhibition of capillary network formation. Furthermore, morphine stimulated other biological functions of HLT-EC under serum deprivation and H2 O2 -induced pathological conditions, such as growth, migration and survival, without affecting HLT-EC adhesion. Interestingly, morphine at the same concentration did not affect lung tumour cell growth and survival, suggesting the specific protective role of morphine at low micromolar concentrations on tumour angiogenesis. Using in vivo Matrigel angiogenesis assay, it was found that morphine stimulated in vivo angiogenesis under H2 O2 -induced pathological condition. The opioid receptor antagonist, naloxone, did not inhibit the protective activity of morphine in in vivo angiogenesis, indicating that the effect was less likely to be mediated by the typical opioid receptors. Mechanism analysis indicated that morphine alleviated serum deprivation and H2 O2 -induced angiogenesis inhibition via reducing oxidative stress and damage, and activating Akt/mTOR/eIF4E signalling. We demonstrate the protective role of morphine on tumour angiogenesis under pathological conditions. Our work suggests that clinical use of morphine may be harmful in patients with angiogenesis-dependent cancers.

LncRNA ZFAS1 serves as a prognostic biomarker to predict the survival of patients with ovarian cancer.

Ovarian cancer (OC) is one of the most fatal types of gynecological malignancy. Certain long non-coding RNAs (lncRNA) have been reported to have crucial roles in cancer progression. Zinc finger nuclear transcription factor, X-box binding 1-type containing 1 antisense RNA 1 (ZFAS1) is a novel regulator lncRNA in various cancer types. The expression pattern of most lncRNAs, including ZFAS1, in OC remains to be determined. In the present study, it was demonstrated that ZFAS1 was overexpressed in OC vs. normal cell lines. However, ZFAS1 was downregulated in OC compared with normal samples in the GEPIA dataset. Furthermore, OC samples of higher stages (stage III/IV) had higher levels of ZFAS1 compared with those in early-stage OC (stage I/II) samples. Of note, higher ZFAS1 expression was associated with shorter overall survival time and disease-free survival time of OC patients. Protein-protein interaction networks of proteins co-expressed with ZFAS1 in OC were constructed. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of genes co-expressed with ZFAS1 indicated that ZFAS1 is associated with translation, mRNA splicing, cell-cell adhesion, DNA repair, protein sumoylation, positive regulation of GTPase activity and DNA replication. The present study may provide novel clues to validate ZFAS1 as a biomarker in OC.

Comparison of epidural anesthesia with chloroprocaine and lidocaine for outpatient knee arthroscopy.

This study aimed to compare clinical efficacy and safety of chloroprocaine and lidocaine in epidural anesthesia for outpatient knee arthroscopy. Eighty patients undergoing knee arthroscopy were randomly allocated to receive 3% 2-chloroprocaine (group C, n = 40) or 2% lidocaine (group L, n = 40) for epidural block. Latency to anesthesia onset, highest block level, time to achieve peak effect, time to complete sensory and motor block regression, vital signs including respiration and hemodynamics, and complications during follow-up were recorded. No significant differences were found in the latency to anesthesia onset and peak effect, duration of anesthesia efficacy, and the time for recovery of sensory function between the two groups. However, the latency to maximal block of pain sensation and the time needed to recover motor function were significantly shorter in group C than in group L (p < 0.05). No adverse effects or neurologic complications were found in both groups. In conclusion, epidural chloroprocaine elicits rapid anesthetic effects, fast sensor and motor block, and faster recovery of motor function compared to lidocaine. These characteristics make chloroprocaine better than lidocaine as the choice of epidural anesthesia in short clinical operations such as knee arthroscopy.

Inhibition of gastric cancer by local anesthetic bupivacaine through multiple mechanisms independent of sodium channel blockade.

BACKGROUND: Retrospective studies of patients undergoing cancer surgery suggest the use of local anesthesia may decrease tumor recurrence and improve survival. The mechanisms on the benefits of local anesthesia on cancer recurrence are complex and remain to be elucidated. METHODS: This study investigated the effects of bupivacaine on various cellular activities of gastric cancer using proliferation, migration, apoptosis assay. The underlying mechanism was analyzed focusing on mitochondrial functions and the activities of Rho family members. RESULTS: We show that bupivacaine at low concentrations (eg, 0.01 and 0.05 mM) inhibits migration whereas only at high concentrations (1 and 5 mM) inhibits growth and survival in two human gastric cancer cell lines. Bupivacaine also significantly augments 5-Fluorouracil in inhibiting growth and survival but not migration in gastric cancer cells. In addition, the mechanisms of bupivacaine's action on the growth and survival are different from those on the migration. We demonstrate that bupivacaine inhibits gastric cancer cell growth and survival through inhibiting mitochondrial respiratory complex I and II, leading to decreased mitochondrial oxidation and ATP production. In contrast, bupivacaine inhibits gastric cancer cell migration through decreasing RhoA and Rac1 activities without affecting their expression. Particularly, we demonstrate that bupivacaine inhibits gastric cancer cell migration via inhibiting RhoA/ROCK/MLC pathway. We further show that the action of bupivacaine on mitochondrial functions, RhoA, and Rac1 activities are independent of sodium channel blockade. CONCLUSIONS: Our work demonstrates that bupivacaine has direct anti-cancer activities with the dominant inhibitory effects on gastric cancer migration rather than growth and survival. Our findings also guide a proper understanding and provide underlying mechanisms on how local aesthesis could affect cancer patients.