Trans-Defect Underlay Watertight Duraplasty for Traumatic Anterior Skull Base Dural Defect: Technical Report.

BACKGROUND: Watertight duraplasty is essential for surgical management of traumatic anterior skull base (ASB) dural defect but challenging in the deep and narrow operative corridor. Here, the authors report a trans-defect underlay watertight duraplasty (TDUWD) technique for traumatic ASB dural defect. METHODS: TDUWD was performed by inserting a free pericranium graft under the dural defect. The diameter of the pericranium graft was larger than the dural defect. The pericranium graft was sutured to the dural defect watertightly in an "inside-to-outside" direction, with the needle not penetrating the inner layer of pericranium graft. The pedicled pericranium flap was used as a second layer of reconstruction. The characteristics, complications, and outcomes of patients who received TDUWD are reported. RESULTS: A total of 29 patients received TDUWD. Immediate postoperative cessation of cerebrospinal fluid (CSF) leak occurred in 28 patients. One patient recovered after lumber drainage. No patient needed a second operation or reported delayed recurrence of CSF leak. No complication related to the surgical technique was observed. CONCLUSIONS: Use of TDUWD for traumatic ASB dural defect results in an immediate, 1-stage, and definitive correction of CSF leak and seems to be simple, safe, and reliable for large and deeply located dural defects.

Exosomal ERBB2IP contributes to tumor growth via elevating PSAT1 expression in non-small cell lung carcinoma.

BACKGROUND: Both exosomes and circular RNAs (circRNAs) are involved in tumor growth. Hsa_circ_0001492 (circERBB2IP) has been reported to be overexpressed in plasma exosomes from patients with lung adenocarcinoma, but the biological role of exosomal circERBB2IP in non-small cell lung carcinoma (NSCLC) is indistinct. METHODS: Exosomes isolated from serums and medium samples were validated by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. Relative expression of circERBB2IP was detected by RT-qPCR. Loss-of-function was done to determine the effect of circERBB2IP on NSCLC cell proliferation and migration. Molecular mechanisms associated with circERBB2IP were predicted by bioinformatic analysis and validated by dual-luciferase reporter, RIP, and RNA pulldown assays. In vivo experiments were performed to identify the function of circERBB2IP in NSCLC. RESULTS: We discovered that circERBB2IP expression was correlated with TNM grade, lymph node metastasis and tumor size of NSCLC patients. Upregulation of circERBB2IP was observed in exosomes derived from NSCLC patient's serum and circERBB2IP might be a potential diagnostic biomarker for NSCLC. CircERBB2IP was transmitted between carcinoma cells through exosomes. Knockdown of circERBB2IP lowered cell growth in mouse models and restrained NSCLC cell proliferation and migration. CircERBB2IP could mediate PSAT1 expression via sponging miR-5195-3p. CONCLUSION: In conclusion, circERBB2IP may drive NSCLC growth by the miR-5195-3p/PSAT1 axis in NSCLC, shedding light on a diagnostic biomarker and therapeutic target for NSCLC.

Intracranial-Pressure-Monitoring-Assisted Management Associated with Favorable Outcomes in Moderate Traumatic Brain Injury Patients with a GCS of 9-11.

Objective: With a mortality rate of 10−30%, a moderate traumatic brain injury (mTBI) is one of the most variable traumas. The indications for intracranial pressure (ICP) monitoring in patients with mTBI and the effects of ICP on patients' outcomes are uncertain. The purpose of this study was to examine the indications of ICP monitoring (ICPm) and its effects on the long-term functional outcomes of mTBI patients. Methods: Patients with Glasgow Coma Scale (GCS) scores of 9−11 at Tangdu hospital, between January 2015 and December 2021, were enrolled and treated in this retrospective cohort study. We assessed practice variations in ICP interventions using the therapy intensity level (TIL). Six-month mortality and a Glasgow Outcome Scale Extended (GOS-E) score were the main outcomes. The secondary outcome was neurological deterioration (ND) events. The indication and the estimated impact of ICPm on the functional outcome were investigated by using binary regression analyses. Results: Of the 350 patients, 145 underwent ICP monitoring-assisted management, and the other 205 patients received a standard control based on imaging or clinical examinations. A GCS ≤ 10 (OR 1.751 (95% CI 1.216−3.023), p = 0.003), midline shift (mm) ≥ 2.5 (OR 3.916 (95% CI 2.076−7.386) p < 0.001), and SDH (OR 1.772 (95% CI 1.065−2.949) p = 0.028) were predictors of ICP. Patients who had ICPm (14/145 (9.7%)) had a decreased 6-month mortality rate compared to those who were not monitored (40/205 (19.5%), p = 0.011). ICPm was linked to both improved neurological outcomes at 6 months (OR 0.815 (95% CI 0.712−0.933), p = 0.003) and a lower ND rate (2 = 11.375, p = 0.010). A higher mean ICP (17.32 ± 3.52, t = −6.047, p < 0.001) and a more significant number of ICP > 15 mmHg (27 (9−45.5), Z = −5.406, p < 0.001) or ICP > 20 mmHg (5 (0−23), Z = −4.635, p < 0.001) 72 h after injury were associated with unfavorable outcomes. The best unfavorable GOS-E cutoff value of different ICP characteristics showed that the mean ICP was >15.8 mmHg (AUC 0.698; 95% CI, 0.606−0.789, p < 0.001), the number of ICP > 15 mmHg was >25.5 (AUC 0.681; 95% CI, 0.587−0.774, p < 0.001), and the number of ICP > 20 mmHg was >6 (AUC 0.660; 95% CI, 0.561−0.759, p < 0.001). The total TIL score during the first 72 h post-injury in the non-ICP group (9 (8, 11)) was lower than that of the ICP group (13 (9, 17), Z = −8.388, p < 0.001), and was associated with unfavorable outcomes. Conclusion: ICPm-assisted management was associated with better clinical outcomes six months after discharge and lower incidences of ND for seven days post-injury. A mean ICP > 15.8 mmHg, the number of ICP > 15 mmHg > 25.5, or the number of ICP > 20 mmHg > 6 implicate an unfavorable long-term prognosis after 72 h of an mTBI.

Predicting Neurological Deterioration after Moderate Traumatic Brain Injury: Development and Validation of a Prediction Model Based on Data Collected on Admission.

Moderate traumatic brain injury (mTBI) is a heterogeneous entity that is poorly defined in the literature. Patients with mTBI have a high rate of neurological deterioration (ND), which is usually accompanied by poor prognosis and no definitive methods to predict. The purpose of this study is to develop and validate a prediction model that estimates the ND risk in patients with mTBI using data collected on admission. Data for 479 patients with mTBI collected retrospectively in our department were analyzed by logistic regression models. Bivariable logistic regression identified variables with a p < 0.05. Multi-variable logistic regression modeling with backward stepwise elimination was used to determine reduced parameters and establish a prediction model. The discrimination efficacy, calibration efficacy, and clinical utility of the prediction model were evaluated. The prediction model was validated using data for 176 patients collected from another hospital. Eight independent prognostic factors were identified: hypertension, Marshall scale (types III and IV), subdural hemorrhage (SDH), location of contusion (frontal and temporal contusions), Injury Severity Score >13, D-dimer level >11.4 mg/L, Glasgow Coma Scale score ≤10, and platelet count ≤152 × 109/L. A prediction model was established and was shown as a nomogram. Using bootstrapping, internal validation showed that the C-statistic of the prediction model was 0.881 (95% confidence interval [CI]: 0.849-0.909). The results of external validation showed that the nomogram could predict ND with an area under the curve of 0.827 (95% CI: 0.763-0.880). The present model, based on simple parameters collected on admission, can predict the risk of ND in patients with mTBI accurately. The high discriminative ability indicates the potential of this model for classifying patients with mTBI according to ND risk.

Management of Postoperative Pain after Elective Craniotomy: A Prospective Randomized Controlled Trial of a Neurosurgical Enhanced Recovery after Surgery (ERAS) Program.

Objective: To prospectively evaluate the efficacy of a neurosurgical enhanced recovery after surgery (ERAS) protocol on the management of postoperative pain after elective craniotomies. Methods: This randomized controlled trial was conducted in the neurosurgical center of Tangdu Hospital (Fourth Military Medical University, Xi'an, China). A total of 129 patients undergoing craniotomies between October 2016 and July 2017 were enrolled in a randomized clinical trial comparing an ERAS protocol to a conventional postoperative care regimen. The primary outcome was the postoperative pain score assessed by a verbal numerical rating scale (NRS). Results: Patients in the ERAS group had a significant reduction in their postoperative pain scores on POD 1 compared to patients in the control group (p < 0.05). More patients (n = 44, 68.8%) in the ERAS group experienced mild pain (NRS: 1 to 3) on POD1 compared with patients (n = 23, 35.4%) in the control group (p < 0.05). A further reduction in pain scores was also observed on POD 2 and maintained on POD 3 in the ERAS group compared with that in the control group. In addition, the median postoperative length of hospital stay was significantly decreased with the incorporation of the ERAS protocol compared to controls (ERAS: 4 days, control: 7 days, P<0.001). Conclusion: The implementation of a neurosurgical ERAS protocol for elective craniotomy patients has significant benefits in alleviating postoperative pain and enhancing recovery leading to early discharge after surgery compared to conventional care. Further evaluation of this protocol in larger, multi-center studies is warranted.

Ambulatory Surgery Protocol for Endoscopic Endonasal Resection of Pituitary Adenomas: A Prospective Single-arm Trial with Initial Implementation Experience.

Endoscopic endonasal transsphenoidal resection has been accepted as a routine therapy for pituitary adenoma, but the postoperative hospital stay is typically several days long. With the advantages of reduced cost and improved patient satisfaction, the application of ambulatory surgery (AS) has developed rapidly. However, AS was still rarely adopted in neurosurgery. Here we designed an AS treatment protocol for pituitary adenoma with the endoscopic endonasal approach (EEA), and reported our initial experiences regarding the safety and efficacy of the AS protocol. 63 patients who presented with pituitary adenoma were screened at the Department of Neurosurgery, Tangdu Hospital from July to September, 2017. A total of 20 pituitary adenoma patients who met the inclusion criteria underwent EEA surgery using this evidence-based AS protocol, which emphasized adequate assessment for eligibility, full preparation to minimize invasiveness, enhanced recovery, and active perioperative patient education. Of the 20 patients enrolled, 18 were discharged on the afternoon of the operation day with a median total length of stay (LOS) of 31 hours (range, 29-32) hours. The median LOS after surgery was 6.5 (range, 5-8) hours. Two patients were transferred from the AS protocol to conventional care due to intraoperative cerebrospinal fluid leakage (one case) and an unsatisfying post-anesthetic discharge score (one case). Complications included transient and reversible mild postoperative nausea and vomiting [visual analog scale (VAS) score <3], headache (VAS score <3) after the operation or early after discharge. No patient was readmitted. Our results supported the safety and efficacy of the AS protocol for pituitary adenoma patients undergoing EEA resection among eligible patients, and further evaluation of this protocol in controlled studies with a larger sample size is warranted.

Successful implementation of an enhanced recovery after surgery (ERAS) protocol reduces nausea and vomiting after infratentorial craniotomy for tumour resection: a randomized controlled trial.

BACKGROUND: Infratentorial craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). Enhanced Recovery After Surgery (ERAS) protocols have been shown in multiple surgical disciplines to improve outcomes, including reduced PONV. However, very few studies have described the application of ERAS to infratentorial craniotomy. The aim of this study was to examine whether our ERAS protocol for infratentorial craniotomy could improve PONV. METHODS: We implemented an evidence-based, multimodal ERAS protocol for patients undergoing infratentorial craniotomy. A total of 105 patients who underwent infratentorial craniotomy were randomized into either the ERAS group (n = 50) or the control group (n = 55). Primary outcomes were the incidence of vomiting, nausea score, and use of rescue antiemetic during the first 72 h after surgery. Secondary outcomes included postoperative anxiety level, sleep quality, and complications. RESULTS: Over the entire 72 h post-craniotomy observation period, the cumulative incidence of vomiting was significantly lower in the ERAS group than in the control group. Meanwhile, the incidence of vomiting was significantly lower in the ERAS group on postoperative days (PODs) 2 and 3. Notably, the proportion of patients with mild nausea (VAS 0-4) was higher in the ERAS group as compared to the control group on PODs 2 or 3. Additionally, the postoperative anxiety level and quality of sleep were significantly better in the ERAS group. CONCLUSION: Successful implementation of our ERAS protocol in infratentorial craniotomy patients could attenuate postoperative anxiety, improve sleep quality, and reduce the incidence of PONV, without increasing the rate of postoperative complications. TRIAL REGISTRATION: ChiCTR-INR-16009662, 27 Oct 2016, Clinical study on the development and efficacy evaluation of Enhanced Recovery After Surgery (ERAS) in Neurosurgery.

Enhanced Recovery After Intraspinal Tumor Surgery: A Single-Institutional Randomized Controlled Study.

OBJECTIVE: To evaluate the safety and efficacy of an enhanced recovery after surgery (ERAS) program for intraspinal tumors in a single-institutional prospective randomized controlled trial. METHODS: A multimodal and multidisciplinary ERAS protocol for intraspinal tumor surgery was developed. A total of 94 enrolled patients were randomized into 2 groups: 48 were managed following the ERAS protocol (ERAS group), and 46 received conventional perioperative care (control group). The primary end point was postoperative length of stay (LOS). The secondary outcomes included postoperative pain score and pain medication use, urinary catheterization, ambulation, mortality, reoperation/readmission rates, complication rates, patient satisfaction, and overall cost. RESULTS: A significant reduction in LOS was achieved in patients undergoing ERAS protocol compared with the controls (5 vs. 8 days; P < 0.0001). Moreover, patients in the ERAS group had better postoperative pain scores (1.0 ± 1.3 vs. 1.9 ± 1.3; P = 0.007), decreased use of patient-controlled analgesia (4.2% vs. 19.6%; P = 0.020) and oral opioid (37.5% vs. 58.7%; P = 0.040), early urinary catheter removal (58.3% vs. 6.5%; P < 0.0001), greater ambulation (68.8% vs. 17.4%; P < 0.0001), and higher satisfaction scores (91.8 ± 4.4 vs. 88.2 ± 6.8; P = 0.022) than did the control group. There were no deaths or 30-day readmission/reoperation in both groups, nor did the postoperative complication rates differ between groups. CONCLUSIONS: The ERAS protocol for intraspinal tumor surgery seems to be feasible, effective, and safe in shortening postoperative LOS, improving postoperative pain control with reduced opioid use, and accelerating functional recovery without increasing rates of complications or reoperation/readmission. Adoption of spine ERAS programs could be encouraged in practice, although validation with larger-scale multicenter trials is warranted.

Tonsillectomy with modified reconstruction of the cisterna magna with and without craniectomy for the treatment of adult Chiari malformation type I with syringomyelia.

BACKGROUND: In light of the controversies regarding the surgical treatment of adult Chiari malformation type I (CM-I) with syringomyelia, a retrospective study was conducted to evaluate the safety and efficacy of tonsillectomy followed by modified reconstruction of the cisterna magna with or without craniectomy. METHODS: Between 2008 and 2017, 78 adult CM-I patients (36 males and 42 females, mean age 40.6 years old) with syringomyelia were treated with posterior fossa decompression (PFD) with tonsillectomy and modified reconstruction of the cisterna magna. Patients were divided into two study groups: group A (n = 40) underwent cranioplasty with replacement of the bone flap; group B (n = 38) underwent suboccipital craniectomy. Neurological outcomes were evaluated by traditional physician assessment (improved, unchanged, and worsened) and the Chicago Chiari Outcome Scale (CCOS). Syringomyelia outcomes were assessed radiologically. RESULTS: The procedure was successfully performed in all patients, and restoration of normal cerebrospinal fluid (CSF) flow was confirmed by intraoperative ultrasonography. The median postoperative follow-up was 20.3 months (range 18-60 months). Clinical improvement was evident in 66 (84.6%) patients, with no significant differences between the two groups (85.0% vs. 84.2%, P = 0.897). According to the CCOS, 36 patients (90.0%) in group A were labeled as "good" outcome, compared with that of 34 (86.8%) in group B (P = 0.734). Improvement of syringomyelia was also comparable between the groups, which was observed in 35 (87.5%) vs. 33 (86.8%) patients (P = 0.887). The postoperative overall (7.5% vs. 23.7%, P = 0.048) and CSF-related (2.5% vs. 18.4%, P = 0.027) complication rates were significantly lower in group A than group B. CONCLUSIONS: Tonsillectomy with modified reconstruction of the cisterna magna without craniectomy seems to be a safe and effective surgical option to treat adult CM-I patients with syringomyelia, though future well-powered prospective randomized studies are warranted to validate these findings.

Neurosurgical enhanced recovery after surgery (ERAS) programme for elective craniotomies: are patients satisfied with their experiences? A quantitative and qualitative analysis.

OBJECTIVE: To evaluate patient satisfaction and associated predictors at discharge, as well as patient experience at 30-day follow-up, in a neurosurgical enhanced recovery after surgery (ERAS) programme. DESIGN: A single-centre, prospective, randomised controlled study. SETTING: A tertiary hospital in China. PARTICIPANTS: A total of 140 neurosurgical patients aged 18-65 years old who had a single intracranial lesion and were admitted for elective craniotomy between October 2016 and July 2017 were included. INTERVENTIONS: Patients were randomised into two groups: 70 patients received care according to a novel neurosurgical ERAS protocol (ERAS group) and 70 patients received conventional perioperative care (control group). OUTCOME MEASURES: Patient satisfaction at discharge was evaluated using a multimodal questionnaire. A secondary analysis of patient experience regarding participation in the ERAS programme was conducted using a semistructured qualitative interview via telephone at 30-day follow-up. RESULTS: The mean patient satisfaction was significantly higher in the ERAS group than in the control group at discharge (92.2±4.3 vs 86.8±7.4, p=0.0001). The most important predictors of patient satisfaction included age (OR=6.934), postoperative nausea and vomiting (PONV) Visual Analogue Scale (VAS) score (OR=0.184), absorbable skin suture (OR=0.007) and postoperative length of stay (LOS) (OR=0.765). Analysis on patient experience revealed five themes: information transfer, professional support, shared responsibility and active participation, readiness for discharge, and follow-up, all of which are closely related and represent positive and negative aspects. CONCLUSIONS: Measures that include decreasing PONV VAS score, incorporating absorbable skin suture and shortening LOS seem to increase patient satisfaction in a neurosurgical ERAS programme. Analysis of data on patient experience highlights several aspects to achieve patient-centred and high-quality care. Further studies are warranted to standardise the assessment of patient satisfaction and experience in planning, employing and appraising the ERAS programme. TRIAL REGISTRATION NUMBER: ChiCTR-INR-16009662.

A randomized controlled study of preoperative oral carbohydrate loading versus fasting in patients undergoing elective craniotomy.

OBJECT: The aim of this study was to evaluate the effect of preoperative oral carbohydrate loading versus fasting on the outcomes of patients undergoing elective craniotomy. METHODS: In a single-center randomized controlled study, 120 neurosurgical patients who were admitted for elective craniotomy were included and randomized into 2 groups: 58 patients received 400 mL of oral carbohydrate loading 2 h before surgery (intervention group), and 62 patients were fasting for 8 h prior to surgery as routine management (control group). The primary end point was glucose homeostasis. Secondary outcomes included handgrip strength, pulmonary function and postoperative complications. RESULTS: Better glucose homeostasis (5.6 ± 1.0 mmol/L vs. 6.3 ± 1.2 mmol/L, P = 0.001) was achieved in patients who received preoperative oral carbohydrate loading compared to fasting. Furthermore, patients in the intervention group had better handgrip strength (25.3 ± 7.1 kg vs. 19.9 ± 7.5 kg, P < 0.0001) and pulmonary function (in terms of peak expiratory flow rate) (315.8 ± 91.5 L/min vs. 270.0 ± 102.7 L/min, P = 0.036) compared to the controls postoperatively. The rates of postoperative surgical and non-surgical complications did not differ between the groups. Both postoperative and total hospital length of stay (LOS) reduced significantly in the intervention group (-3d, P < 0.0001 and P = 0.004). CONCLUSIONS: Oral carbohydrate loading given 2 h before surgery in patients undergoing elective craniotomy seems to improve glucose homeostasis, handgrip strength and pulmonary function as well as decrease LOS without increasing the risk of postoperative complications. Routine use of preoperative oral carbohydrate loading could be suggested in clinical settings, though further evaluation of its safety and efficacy is warranted.

Safety and efficacy of a novel neurosurgical enhanced recovery after surgery protocol for elective craniotomy: a prospective randomized controlled trial.

OBJECTIVEAlthough enhanced recovery after surgery (ERAS) programs have gained acceptance in various surgical specialties, no established neurosurgical ERAS protocol for patients undergoing elective craniotomy has been reported in the literature. Here, the authors describe the design, implementation, safety, and efficacy of a novel neurosurgical ERAS protocol for elective craniotomy in a tertiary care medical center located in China.METHODSA multidisciplinary neurosurgical ERAS protocol for elective craniotomy was developed based on the best available evidence. A total of 140 patients undergoing elective craniotomy between October 2016 and May 2017 were enrolled in a randomized clinical trial comparing this novel protocol to conventional neurosurgical perioperative management. The primary endpoint of this study was the postoperative hospital length of stay (LOS). Postoperative morbidity, perioperative complications, postoperative pain scores, postoperative nausea and vomiting, duration of urinary catheterization, time to first solid meal, and patient satisfaction were secondary endpoints.RESULTSThe median postoperative hospital LOS (4 days) was significantly shorter with the incorporation of the ERAS protocol than that with conventional perioperative management (7 days, p < 0.0001). No 30-day readmission or reoperation occurred in either group. More patients in the ERAS group reported mild pain (visual analog scale score 1-3) on postoperative day 1 than those in the control group (79% vs. 33%, OR 7.49, 95% CI 3.51-15.99, p < 0.0001). Similarly, more patients in the ERAS group had a shortened duration of pain (1-2 days; 53% vs. 17%, OR 0.64, 95% CI 0.29-1.37, p = 0.0001). The urinary catheter was removed within 6 hours after surgery in 74% patients in the ERAS group (OR 400.1, 95% CI 23.56-6796, p < 0.0001). The time to first oral liquid intake was a median of 8 hours in the ERAS group compared to 11 hours in the control group (p < 0.0001), and solid food intake occurred at a median of 24 hours in the ERAS group compared to 72 hours in the control group (p < 0.0001).CONCLUSIONSThis multidisciplinary, evidence-based, neurosurgical ERAS protocol for elective craniotomy appears to have significant benefits over conventional perioperative management. Implementation of ERAS is associated with a significant reduction in the postoperative hospital stay and an acceleration in recovery, without increasing complication rates related to elective craniotomy. Further evaluation of this protocol in large multicenter studies is warranted.Clinical trial registration no.: ChiCTR-INR-16009662 (chictr.org.cn).

Endoscopic Endonasal Approach to Mesencephalic Cavernous Malformations.

BACKGROUND: Symptomatic cavernous malformations involving the brainstem are difficult to access by conventional approaches, which often require dramatic brain retraction to gain adequate operative corridor. Here, we present a successful endoscopic endonasal transclival approach for resection of a hemorrhagic, symptomatic mesencephalic cavernous malformation. CASE DESCRIPTION: A 20-year-old woman presented with acute onset of headache, nausea, and vomiting. Computed tomography scan revealed a ventral midbrain hemorrhage. On day 3 of admission, the patient developed left-sided hemiparesis, restriction of medial and lateral left-eye movements, and loss of left pupillary light reflex. Subsequent magnetic resonance imaging demonstrated an increase of the midbrain lesion to 1.2 cm × 1.7 cm. Diffusion tensor imaging showed compression and lateral displacement of the right corticospinal tract near the thalamus and cerebral peduncle. Given the patient's clinical presentation and the findings on imaging, we suspected a mesencephalic cavernous malformation. CONCLUSIONS: The patient underwent an endoscopic endonasal transclival resection of a ventral midline mesencephalon cavernous malformation. A dark red lesion was directly visualized under the endoscope. After a small cortiectomy, the pial and perforator vessels were dissected, and dark-brown blood was drained from the cavernoma cavity. Using a biopsy forceps and with careful attention to the cavernoma borders, the lesion was removed and hemostasis was achieved. Pathologic examination confirmed cavernous malformation. One week after the operation, magnetic resonance imaging demonstrated total resection of the lesion. A 3-month follow-up revealed improved neurologic symptoms with minimal surgical morbidity.

Critical roles of chemokine receptor CCR5 in regulating glioblastoma proliferation and invasion.

Glioblastoma (GBM) is the most prevalent malignant primary brain tumor in adults and exhibits a spectrum of aberrantly aggressive phenotype. Tumor cell proliferation and invasion are critically regulated by chemokines and their receptors. Recent studies have shown that the chemokine CCL5 and its receptor CCR5 play important roles in tumor invasion and metastasis. Nonetheless, the roles of the CCR5 in GBM still remain unclear. The present study provides the evidence that the chemokine receptor CCR5 is highly expressed and associated with poor prognosis in human GBM. Mechanistically, CCL5-CCR5 mediates activation of Akt, and subsequently induces proliferation and invasive responses in U87 and U251 cells. Moreover, down-regulation of CCR5 significantly inhibited the growth of glioma in U87 tumor xenograft mouse model. Finally, high CCR5 expression in GBM is correlated with increased p-Akt expression in patient samples. Together, these findings suggest that the CCR5 is a critical molecular event associated with gliomagenesis.

Exogenous hydrogen sulfide exhibits anti-cancer effects though p38 MAPK signaling pathway in C6 glioma cells.

It has been documented that H2S, in some types of cancer, promotes tumor proliferation, whereas, in the other types, it inhibits the tumor cell growth. In the present study, we investigated the anti-cancer effects and relevant mechanisms of NaHS in C6 glioma cells. C6 cells were subjected to different concentrations of NaHS, then cell viability and morphological changes were examined by MTT assay and Hoechst staining. The protein expression of Caspase-3, Bcl-2, Bax, p38 MAPK (mitogen-activated protein kinase), and p53 was measured by Western blotting. This work demonstrated that NaHS could reduce cell number and induce apoptosis of C6 gliomas cells. The protein expression of Caspase-3 and Bax was up-regulated, while the protein expression of Bcl-2 was down-regulated. Additionally, p38 MAPK and p53 were activated in response to NaHS. Moreover, p38 MAPK inhibitor, SB203580, counteracted the inhibitory effect of NaHS on C6 glioma cells. These data suggest that NaHS can effectively reduce cell number of C6 cells by triggering the apoptosis via Caspase-dependent pathway. p38 MAPK and p53 play an important role in NaHS-induced apoptosis in C6 cells. These findings imply that administration of NaHS may represent a new strategy for the treatment of glioma.