ebv-circRPMS1 promotes the progression of EBV-associated gastric carcinoma via Sam68-dependent activation of METTL3.

Epstein-Barr virus (EBV) is a tumor virus that is associated with a variety of neoplasms, including EBV-associated gastric carcinoma (EBVaGC). Recently, EBV was reported to generate various circular RNAs (circRNAs). CircRNAs are important regulators of tumorigenesis by modulating the malignant behaviors of tumor cells. However, to date, the functions of ebv-circRNAs in EBVaGC remain poorly understood. In the present study, we observed high ebv-circRPMS1 expression in EBVaGC and showed that ebv-circRPMS1 promoted the proliferation, migration, and invasion and inhibited the apoptosis of EBVaGC cells. In addition, METTL3 was upregulated in GC cells overexpressing ebv-circRPMS1. Mechanistically, ebv-circRPMS1 bound to Sam68 to facilitate its physical interaction with the METTL3 promotor, resulting in the transactivation of METTL3 and cancer progression. In clinical EBVaGC samples, ebv-circRPMS1 was associated with distant metastasis and a poor prognosis. Based on these findings, ebv-circRPMS1 contributed to EBVaGC progression by recruiting Sam68 to the METTL3 promoter to induce METTL3 expression. ebv-circRPMS1, Sam68, and METTL3 might serve as therapeutic targets for EBVaGC.

Hypoxia-induced ebv-circLMP2A promotes angiogenesis in EBV-associated gastric carcinoma through the KHSRP/VHL/HIF1α/VEGFA pathway.

EBV-encoded circular RNA LMP2A (ebv-circLMP2A) was found to be expressed in EBV-associated gastric carcinoma (EBVaGC) and associated with distant metastasis and poor prognosis. Angiogenesis is a key step in tumor invasion and metastasis and plays a crucial role in tumor progression. However, it is unclear whether and how ebv-circLMP2A is involved in angiogenesis. In this study, we showed that MVD, HIF1α, and VEGFA expression was increased in EBVaGC mouse xenografts with high expression of ebv-circLMP2A. The expression of ebv-circLMP2A was positively correlated with MVD, HIF1α, and VEGFA expression in clinical samples of EBVaGC. Knockdown of ebv-circLMP2A repressed tube formation and migration of HUVECs and decreased VEGFA and HIF1α expression in cancer cells under hypoxia, while ectopic expression of ebv-circLMP2A reversed these effects. Additionally, knockdown of HIF1α blocked the upregulation of ebv-circLMP2A by hypoxia, and ebv-circLMP2A interacted with KHSRP to enhance KHSRP-mediated decay of VHL mRNA, leading to the accumulation of HIF1α under hypoxia. There was a positive feedback loop between HIF1α and ebv-circLMP2A that promotes angiogenesis under hypoxia. ebv-circLMP2A was essential in regulating tumor angiogenesis in EBVaGC and might provide a valuable therapeutic target for EBVaGC.

Epstein-Barr virus-derived circular RNA LMP2A induces stemness in EBV-associated gastric cancer.

Cancer stem cells (CSCs) are cancer-initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV-associated gastric cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5-fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU-4th, which displays properties of CSCs and mainly consists of CD44+ CD24- cells. In SNU-4th cells, an EBV-encoded circRNA, ebv-circLMP2A, expression increased and plays crucial roles in inducing and maintaining stemness phenotypes through targeting miR-3908/TRIM59/p53 axis. Additionally, high expression of ebv-circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv-circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC.

Intrathecal delivery of hydromorphone vs morphine for refractory cancer pain: a multicenter, randomized, single-blind, controlled noninferiority trial.

Hydromorphone is an alternative to morphine for intrathecal drug delivery system to treat refractory cancer pain; however, there is not enough clinical evidence to prove it. In our study, 233 patients from 12 different pain management centers across China were enrolled, 121 and 112 in the intrathecal hydromorphone (ITHM) and intrathecal morphine (ITMO) groups, respectively. The primary outcome was the clinical success rate, which was defined as ratio of patients achieving ≥50% pain relief. The noninferiority margin was defined as -0.15. Other outcomes included daily visual analogue scale score, breakthrough pain (BTP) incidence, intrathecal dose change, and patient-controlled analgesia bolus count change, GAD-7/PHQ-9. Clinical success was achieved in 85 and 79 of the 121 ITHM patients (70.2%) and 112 ITMO patients (70.5%), respectively. Compared to the corresponding baseline findings, significantly decreased visual analogue scale scores and BTP incidence were noted in both groups. The dose change rate decreased and increased with time in the ITHM and ITMO groups, respectively (ITHM -3.33% vs ITMO 35.4%, P < 0.01, t test) from the third week. The patient-controlled analgesia bolus change rate was lower in the ITHM group than in the ITMO group (ITHM -19.88% vs ITMO 7.79%, P < 0.01, t test) from first week. Our result shows that ITHM is noninferior to ITMO on pain relief to treat refractory cancer pain, however, at different doses and that the doses of morphine tended to increase, whereas those of hydromorphone decreased over time. Hydromorphone offers advantage over morphine in controlling BTP.

The implication of tumor-infiltrating lymphocytes in Epstein-Barr virus-associated gastric carcinoma.

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a distinct entity that has conspicuously inflammatory infiltration compared with EBV-negative gastric carcinoma. To date, the local immune status in EBVaGC and its relationship with patient prognosis and apoptosis of tumor cells are largely unknown. In this study, we evaluated the density of different types of tumor-infiltrating lymphocytes (TILs) in 53 EBVaGCs and 67 EBV-negative gastric carcinomas and analyzed its relationship with patient outcomes and apoptosis of tumor cells in EBVaGC. The average number of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, CD56+ natural killer cells, Fascin+ dendritic cells (DCs), and FoxP3+ Tregs and the average proportions of Ki-67, interleukin 1ß, granzyme B, interferon γ, and interleukin 10 in TILs were higher in EBVaGC, and CD8+ T cells were the predominant constituent cells of TILs in EBVaGC. Patients with higher numbers of CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs survived longer in EBVaGC, and CD8+ T cells and Fascin+ DCs were independent prognostic factors for patient survival. Besides, CD8+ T cells were positively correlated with apoptotic index of tumor cells. However, the apoptosis of tumor cells was lower, and the expression of survivin and NF-κBp65 in tumor cells was up-regulated in EBVaGC. These findings suggested that CD3+ total T cells, CD8+ T cells, CD79α+ B cells, and Fascin+ DCs predict a better prognosis in EBVaGC; CD8+ T cells might through a nonapoptotic pathway eliminate tumor cells, thereby improving the patient prognosis.

Expression of CCL21 by EBV-associated gastric carcinoma cells protects CD8+CCR7+ T lymphocytes from apoptosis via the mitochondria-mediated pathway.

About 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV), which are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are usually accompanied by massive lymphocytes infiltration, among which CD8+ T cells are predominant. To date, the apoptosis of the infiltrating CD8+ T cells in EBVaGC has not been investigated. In the present study, we assessed the immunophenotype and apoptosis of tumour infiltrating lymphocytes (TILs) in both EBVaGC and EBV-negative gastric carcinoma (EBVnGC). We found that CD8+CCR7+ T lymphocytes were increased in EBVaGC compared to EBVnGC [60.53 ± 28.41/high power fields (HPF) vs 19.63 ± 15.97/HPF; p < 0.001]. Moreover, the apoptosis index of TILs was lower in EBVaGC than that in EBVnGC (1.34 ± 0.90 vs 5.94 ± 3.77; p < 0.001). Given that the CCL21-CCR7 axis is reported to be potentially involved in apoptosis, we examined the expression of CCL21 in both EBVaGC and EBVnGC. We found that CCL21 expression was higher in EBVaGC than in EBVnGC (p < 0.001). We also showed that the expression of CCL21 by EBVaGC cells protected CD8+CCR7+ T lymphocytes from apoptosis. Furthermore, the up-regulation of Bcl-2 contributed to the inhibition of apoptosis in CD8+CCR7+ T cells. Collectively, these findings suggest that expression of CCL21 by EBVaGC cells protects CD8+CCR7+ T lymphocytes from apoptosis via the mitochondria-mediated pathway. To our best knowledge, this is the first study to investigate the apoptosis of CD8+ T cells in EBVaGC.

Novel multimodal analgesia regimen improves post-TACE pain in patients with hepatocellular carcinoma.

BACKGROUD: Transarterial chemoembolization (TACE) is the primary palliative treatment for patients with unresectable hepatocellular carcinoma (HCC). However, it is often accompanied by postoperative pain which hinder patient recovery. This study was to examine whether preemptive parecoxib and sufentanil-based patient controlled analgesia (PCA) could improve the pain management in patients receiving TACE for inoperable HCC. METHODS: From June to December 2016, 84 HCC patients undergoing TACE procedure were enrolled. Because of the willingness of the individuals, it is difficult to randomize the patients to different groups. We matched the patients' age, gender and pain scores, and divided the patients into the multimodal group (n = 42) and control group (n = 42). Patients in the multimodal group received 40 mg of parecoxib, 30 min before TACE, followed by 48 h of sufentanil-based PCA. Patients in the control group received a routine analgesic regimen, i.e., 5 mg of dezocine during operation, and 100 mg of tramadol or equivalent intravenous opioid according to patient's complaints and pain intensity. Postoperative pain intensity, percentage of patients as per the pain category, adverse reaction, duration of hospital stay, cost-effectiveness, and patient's satisfaction were all taken into consideration when evaluated. RESULTS: Compared to the control group, the visual analogue scale scores for pain intensity was significantly lower at 2, 4, 6, and 12 h (all P < 0.05) in the multimodal group and a noticeably lower prevalence of post-operative nausea and vomiting in the multimodal group (31.0% vs. 59.5%). Patient's satisfaction in the multimodal group was also significantly higher than that in the control group (95.2% vs. 69.0%). No significant difference was observed in the duration of hospital stay between the two groups. CONCLUSION: Preemptive parecoxib and sufentanil-based multimodal analgesia regime is a safe, efficient and cost-effective regimen for postoperative pain control in HCC patients undergoing TACE.

Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids: Case Report and Review of the Literature.

The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No optimal treatment for such metastases has yet been defined.

Accumulation Mechanisms of CD4(+)CD25(+)FOXP3(+) Regulatory T Cells in EBV-associated Gastric Carcinoma.

Approximately 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV) and are defined as EBV-associated gastric carcinomas (EBVaGCs). EBVaGCs are known to be accompanied by massive CD8(+) cytotoxic T cell (CTL) infiltration; however, adoptive cellular immunotherapy based on EBV-specific CD8(+) CTLs has been explored with limited success. Because regulatory T cells (Tregs) are regarded as a critical hurdle in anti-tumour immunity, we assessed the distribution of Tregs in 45 cases of EBVaGC and 45 cases of EBV-negative gastric carcinoma (EBVnGC) with matched clinicopathological parameters by immunohistochemistry. We showed that Tregs were significantly increased in EBVaGC compared to EBVnGC (15.92 ± 11.45/HPF vs. 8.45 ± 6.16/HPF, p = 0.001). In addition, we explored the accumulation mechanisms of Tregs in EBVaGC by using EBV (+) gastric carcinoma cell lines SNU719 and GT39 as ex vivo models. When peripheral blood mononuclear cells (PBMCs) were co-cultured with EBV (+) gastric carcinoma cell lines, the Treg frequency increased, and they underwent phenotypic and functional changes. The enhanced recruitment by CCL22 produced by EBVaGC cells, the decreased emigration due to CCR7 downregulation on the Treg surface, the higher proliferation rate, and the lower apoptosis rate of Tregs at tumour sites may promote the accumulation of Tregs in EBVaGC.

Sonic hedgehog signalling pathway regulates apoptosis through Smo protein in human umbilical vein endothelial cells.

OBJECTIVE: The aim of this study was to investigate the expression of smoothened protein (Smo), a sonic hedgehog (Shh) signalling component, in synovium of RA and its role in the survival and apoptosis of endothelial cells. METHODS: The expression of Smo pxrotein in RA synovial tissue was examined by immunohistochemistry. Real-time PCR and western blotting techniques were employed to measure the expression of Shh signalling components in EA.hy926 endothelial cells exposed to TNF-α in the presence or absence of cyclopamine (a Smo-specific antagonist). Lastly, the effect of cyclopamine and Smo small interfering RNA on apoptosis induced by TNF-α and actinomycin D (ActD) was determined. RESULTS: We found that Smo was highly expressed in synovial tissues of RA, especially in endothelial cells, compared with the trauma group. TNF-α significantly increased the expression of Shh signalling components in EA.hy926 endothelial cells, while cyclopamine decreased the expression of Shh signalling components. EA.hy926 endothelial cells treated with various concentrations of cyclopamine (2-8 µmol/l) showed a significant decrease in cell viability and cell survival rate, and an increase in the rate of cell apoptosis compared with endothelial cells treated with TNF-α and ActD (P < 0.05). EA.hy926 endothelial cells transfected with Smo-siRNA also showed a lower cell survival rate and higher apoptotic rate, compared with cells in the control group (P < 0.05). CONCLUSION: The Shh signalling pathway plays a role in regulating endothelial cell apoptosis in a Smo-dependent manner.

OPN and αvß3 expression are predictors of disease severity and worse prognosis in hepatocellular carcinoma.

Expressions of OPN and αvß3 are associated with a poor prognosis in many malignancies. However, their relationship in hepatocellular carcinoma remains unclear. We systematically collected hepatocellular carcinoma tissue samples from 305 patients over 3 years, and analyzed the status of OPN and αvß3 in hepatocellular carcinoma and correlate expression with patient disease status and survival outcome. Our study results indicated that OPN and αvß3 are expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent non-tumorous tissue (69.5% vs 18.4%, p<0.01 and 77.4% vs 21.6%, p<0.01, respectively). Both OPN and αvß3 expression levels are associated with poor prognostic factors, including tumor size, capsular invasion, tumor thrombus of the portal vein, metastasis of the lymph node and clinical staging. Patients expressing OPN and αvß3 had significantly shorter survival compared with patients negative for protein expression (p<0.01). Multivariate analysis also showed that both OPN and αvß3 expression are independent prognostic factors for poorer survival in hepatocellular carcinoma. By this study, we conclude that OPN and αvß3 are negative prognostic predictors in patients with hepatocellular carcinoma. The expressions of both OPN and αvß3 are associated with worse survival outcome.

Increased severity of inflammation correlates with elevated expression of TRPV1 nerve fibers and nerve growth factor on interstitial cystitis/bladder pain syndrome.

OBJECTIVES: Although evidence supports a role for inflammation in interstitial cystitis/bladder pain syndrome (IC/BPS), the mechanism remains unknown. We determined whether inflammation causes an elevated expression of nerve growth factor (NGF) and transient receptor potential vanilloid receptor subtype 1 (TRPV1) and correlated them with the symptoms. METHODS: Bladder biopsies were obtained from 53 IC/BPS patients and 27 controls, and hematoxylin and eosin staining, immunostaining and Western blotting were performed to detect inflammation, TRPV1-immunoreactive and PGP9.5-immunoreactive nerve fibers, and NGF, respectively. Symptoms were assessed using the Pelvic Pain/Urgency/Frequency (PUF) questionnaire and pain visual analogue scale scores. Suburothelial nerve fiber density was quantified and correlated with PUF scores. RESULTS: Increased severity of inflammation was correlated with a higher TRPV1-immunoreactive nerve fiber density (r = 0.4113, p = 0.0024) and higher NGF levels (r = 0.3775, p = 0.0052). Suburothelial TRPV1-immunoreactive nerve fiber density was significantly correlated with pain scores and urgency scores (r = 0.3320, p = 0.0145 and r = 0.3823, p = 0.0039, respectively). PGP9.5-immunoreactive nerve fibers were significantly increased in IC/BPS (p = 0.0193) and had a positive relationship with inflammation severity (r = 0.6138, p < 0.0001). CONCLUSIONS: Our study revealed increased severity of inflammation correlated with a higher expression of TRPV1-immunoreactive nerve fibers and NGF in IC/BPS and correlated with clinical symptoms.

Goal-directed fluid optimization based on stroke volume variation and cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations: a pilot study.

OBJECTIVES: This pilot study was designed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies. METHODS: Eighty patients undergoing thoracoscopic lobectomy were randomized into either a goal-directed therapy group or a control group. In the goal-directed therapy group, the stroke volume variation was controlled at 10%±1%, and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2. In the control group, the MAP was maintained at between 65 mm Hg and 90 mm Hg, heart rate was maintained at between 60 BPM and 100 BPM, and urinary output was greater than 0.5 mL/kg-1/h-1. The hemodynamic variables, arterial blood gas analyses, total administered fluid volume and side effects were recorded. RESULTS: The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal-directed therapy group was significantly higher than that of the control group, but there were no differences between the goal-directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia. The extubation time was significantly earlier in the goal-directed therapy group, but there was no difference in the length of hospital stay. Patients in the control group had greater urine volumes, and they were given greater colloid and overall fluid volumes. Nausea and vomiting were significantly reduced in the goal-directed therapy group. CONCLUSION: The results of this study demonstrated that an optimization protocol, based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device, increased the PaO2/FiO2-ratio and reduced the overall fluid volume, intubation time and postoperative complications (nausea and vomiting) in thoracic surgery patients requiring one-lung ventilation.

Goal-directed fluid optimization based on stroke volume variation and cardiac index during one-lung ventilation in patients undergoing thoracoscopy lobectomy operations: a pilot study

OBJECTIVES: This pilot study was designed to utilize stroke volume variation and cardiac index to ensure fluid optimization during one-lung ventilation in patients undergoing thoracoscopic lobectomies. METHODS: Eighty patients undergoing thoracoscopic lobectomy were randomized into either a goal-directed therapy group or a control group. In the goal-directed therapy group, the stroke volume variation was controlled at 10%±1%, and the cardiac index was controlled at a minimum of 2.5 L.min-1.m-2. In the control group, the MAP was maintained at between 65 mm Hg and 90 mm Hg, heart rate was maintained at between 60 BPM and 100 BPM, and urinary output was greater than 0.5 mL/kg-1/h-1. The hemodynamic variables, arterial blood gas analyses, total administered fluid volume and side effects were recorded. RESULTS: The PaO2/FiO2-ratio before the end of one-lung ventilation in the goal-directed therapy group was significantly higher than that of the control group, but there were no differences between the goal-directed therapy group and the control group for the PaO2/FiO2-ratio or other arterial blood gas analysis indices prior to anesthesia. The extubation time was significantly earlier in the goal-directed therapy group, but there was no difference in the length of hospital stay. Patients in the control group had greater urine volumes, and they were given greater colloid and overall fluid volumes. Nausea and vomiting were significantly reduced in the goal-directed therapy group. CONCLUSION: The results of this study demonstrated that an optimization protocol, based on stroke volume variation and cardiac index obtained with a FloTrac/Vigileo device, increased the PaO2/FiO2-ratio and reduced the overall fluid volume, intubation time and postoperative complications (nausea and vomiting) in thoracic surgery patients requiring one-lung ventilation. .

Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression.

BACKGROUND: Propofol is one of the extensively and commonly used intravenous anesthetics and has the ability to influence the proliferation, motility, and invasiveness of many cancer cells. In this study, the effects of propofol on hepatocellular carcinoma cells invasion ability were examined. METHODS: We assessed the invasion ability of HepG2 cells in vitro by determining enzyme activity and protein expression of MMP-9 using gelatin zymography assay and Western blot. The real-time PCR was used to evaluate the effect of propofol on microRNA-199a (miR-199a) expression, and miR-199a-2 precursor to evaluate whether over-expression of miR-199a can affect MMP-9 expression. Finally, the effect of miR-199a on propofol-induced anti-tumor activity using anti-miR-199a was assessed. RESULTS: Propofol significantly elevated the expression of miR-199a and inhibited the invasiveness of HepG2 cells. Propofol also efficiently decreased enzyme activity and protein expression of MMP-9. Moreover, the over-expression of miR-199a decreased MMP-9 protein level. Interestingly, the neutralization of miR-199a by anti-miR-199a antibody reversed the effect of propofol on alleviation of tumor invasiveness and inhibition of MMP-9 activity in HepG2 cells. CONCLUSION: Propofol decreases hepatocellular carcinoma cell invasiveness, which is partly due to the down-regulation of MMP-9 expression by miR-199a.

Propofol induces apoptosis of hepatocellular carcinoma cells by upregulation of microRNA-199a expression.

Propofol is one of the extensively commonly used intravenous anaesthetic agents. The effects of Propofol on hepatocellular carcinoma (HCC) growth inhibition and apoptosis have been examined. The techniques used were the MTT assay, flow cytometry, real-time PCR to assess miR-199a expression, as also caspase-8 and caspase-9 activity in HepG2 cells treated with Propofol. Finally, we evaluated the effect of miR-199a on Propofol-induced anti-tumour activity using anti-miR-199a. Propofol efficiently inhibited the growth of HCC cells, but was less toxic to normal hepatic cells. It induced apoptosis and increased expression of miR-199a. Activation of caspase-8 and caspase-9 suggested that both extrinsic and intrinsic pathways are involved in Propofol-induced apoptosis. Anti-miR-199a reversed the effect of Propofol on apoptosis and activation of caspase-8 and caspase-9 in HepG2 cells. Propofol can effectively induce apoptosis of HCC cells and modulation of miR-199a possibly contributes to the anti-tumour action of Propofol. Hence, Propofol might be an effective drug for HCC.

Overexpression of osteopontin, αvß3 and Pim-1 associated with prognostically important clinicopathologic variables in non-small cell lung cancer.

In this study, we examined the expression of osteopontin (OPN), αvß3 and Pim-1 in non-small cell lung cancer (NSCLC) and investigated the potential clinical implications of their expression patterns in NSCLC. Immunohistochemical assays were used to examine the protein expression of OPN, αvß3 and Pim-1 in 208 NSCLC samples and their adjacent normal lung tissue specimens. Statistical analyses were performed to evaluate the relationships between OPN, αvß3 and Pim-1 expression patterns, and their association with the clinical-pathological parameters of NSCLC patients. In NSCLC tissues, the positive rates of OPN, αvß3 and Pim-1 expression were 67.8% (141/208), 76.0% (158/208) and 58.7% (122/208), respectively. However, in the adjacent normal lung tissues, the positive rates of OPN, αvß3 and Pim-1 were 20.2% (42/208), 24.0% (50/208) and 14.9% (31/208), respectively. The differences in the positive expression rates of OPN, αvß3 and Pim-1 between NSCLCs and the adjacent normal lung tissues were all significant (P<0.01). Additionally, the positive expression of OPN, αvß3 and Pim-1 in NSCLCs was associated with an increase in pathological grade, lymph node metastasis and advanced clinical stage (all P<0.01). Furthermore, associations between the expression of OPN and αvß3, OPN and Pim-1, and αvß3 and Pim-1 were also observed in our NSCLC cohort (all P<0.01). The OPN, αvß3 and Pim-1 proteins are frequently overexpressed in NSCLC and are associated with some clinicopathologic variables that are of known prognostic importance in NSCLC, suggesting that they may play an important role in the development and/or progression of NSCLC.

Epidural fentanyl decreases the minimum local analgesic concentration of epidural lidocaine.

BACKGROUND: Epidural lidocaine can be used when regional anesthesia needs to be established quickly, but the effect of co-administering epidural fentanyl on the minimum local analgesic concentration (MLAC) of lidocaine is not known. We compared the MLAC of epidural lidocaine in combination with different doses of fentanyl for epidural anesthesia in adults. METHODS: One hundred and twenty patients requiring epidural analgesia were randomly allocated to receive 20 ml of one of four solutions: lidocaine, or lidocaine plus fentanyl 1 µg/ml, 2 µg/ml, or 3 µg/ml. The first patient in each group was administered 1% lidocaine weight by volume; subsequent patients received a concentration determined by the response of the previous patient to a higher or lower concentration according to up and down sequential allocation in 0.1% increments. Efficacy was assessed using a visual analog pain scale, and accepted if this was = 10 mm on a 100 mm scale within 30 minutes. The extent of motor block and of nausea and vomiting were recorded at 30 minutes after administration of the epidural solution and two hours after surgery, respectively. RESULTS: The MLAC of lidocaine in those receiving lidocaine alone was 0.785% (95%CI 0.738 - 0.864). A significant dose-dependent reduction was observed with the addition of fentanyl: the MLAC of lidocaine with fentanyl at 2 µg/ml was 0.596% (95%CI 0.537 - 0.660) and 0.387% with fentanyl at 3 µg/ml (95%CI 0.329 - 0.446, P < 0.001). CONCLUSION: Epidural fentanyl significantly reduces the dose of lidocaine required for effective epidural analgesia in adults without causing adverse side effects.

Low expression of Beclin 1, associated with high Bcl-xL, predicts a malignant phenotype and poor prognosis of gastric cancer.

Recent studies have suggested that dysregulation of autophagy plays a pivotal role in tumorigenesis. Here, we determined the prognostic value of autophagy-related protein Beclin 1 in gastric cancer. A total of 153 primary gastric cancer patients were subjected to analysis of Beclin 1 expression and survival prognosis. Among them, 68 patients were assigned randomly and used as a training set to generate a cutoff score for Beclin 1 expression by receive operating characteristic (ROC) curve analysis. The ROC-generated cutoff score was subjected to analyze the association of Beclin 1 with clinical characteristics and patient outcome. In a testing set (n = 85) and overall patients (n = 153), both univariate and multivariate analysis found that low expression of Beclin 1 predicted adverse overall survival and progression-free survival for gastric cancer patients. Furthermore, in each stage of gastric cancer patients, Beclin 1 expression was a prognostic indicator in patients with stage II, III and IV. Importantly, a reverse relationship between Beclin 1 and Bcl-xL expression was demonstrated. In patients of elevated Bcl-xL expression, a subset with lower Beclin 1 expression displayed an inferior overall survival and progression-free survival than those with higher Beclin 1 expression. Thus, our data demonstrated that low expression of Beclin 1, associated with high Bcl-xL, played as an independent biomarker, contributing to a more aggressive cancer cell phenotype and poor prognosis for gastric tumor.