Concurrent mutations of germline GPR101 and somatic USP8 in a pediatric giant pituitary ACTH adenoma: a case report.

BACKGROUND: Cushing's disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD. CASE PRESENTATION: A girl presented at the age of 10 years and 9 months with facial plethora, hirsutism and acne. Her vision and eye movements were impaired. A quick weight gain and slow growth were also observed. Physical examination revealed central obesity, moon face, buffalo hump, supra-clavicular fat pads and bruising. Her plasma ACTH level ranged between 118 and 151 pg/ml, and sella enhanced MRI showed a giant pituitary tumor of 51.8 × 29.3 × 14.0 mm. Transsphenoidal pituitary debulk adenomectomy was performed and immunohistochemical staining confirmed an ACTH-secreting adenoma. Genetic analysis identified a novel germline GPR101 (p.G169R) and a somatic USP8 (p. S719del) mutation. They were hypothesized to impact tumor growth and function, respectively. CONCLUSIONS: We reported a rare case of pediatric giant pituitary ACTH adenoma and pointed out that unusual concurrent mutations might contribute to its early onset and large volume.

[Influence of Nasal Disinfection on Nasal Bacterial Colonization through the Transsphenoidal Approach].

Objective To explore the influence of the iodine disinfection on nasal bacterial colonization through the transsphenoidal approach. Methods Totally 133 pituitary adenoma patients who underwent transsphenoidal surgery in our department from January to August 2017 were enrolled in this study. Before disinfection,pharyngeal swabs of inferior turbinate root secretions were taken for bacterial culture. After iodine disinfection,pharyngeal swabs were taken again at the same site. Changes in the nasal bacterial spectrum before and after disinfection were compared. Patients were followed up for three months after the surgery,during which any intracranial infection/bacteraemia was recorded,and its correlation with nasal bacteria colonization was analyzed. Results Nasal bacterial colonization was detected in 45 (33.8%) of 133 patients before iodine disinfection and in only 6 cases (4.5%) after iodine disinfection (χ2=34.5,P=0.000). Thus,iodine disinfection eliminated 86.7%(39/45) of the colonized bacteria. The most common nasal bacterium was Staphylococcus aureus (24.4%,11/45),followed by Klebsiella pneumoniae (24.4%,11/45),and Staphylococcus epidermidis (13.3%,6/45). One patient had high fever and chills 2 days after surgery,but blood culture and cerebrospinal fluid culture showed negative Results . After the administration of third-generation cephalosporins,the symptoms disappeared after two days. Conclusion sThere are colonized bacteria in nasal cavity. Iodine disinfection of nasal cavity can effectively clear most of the nasal bacteria. The possibility of intracranial infection/bacteremia after transsphenoidal approach is low.

[Association of GH and IGF-1 Burden with Cardiac Structural and Functional Changes in Acromegaly Patients].

OBJECTIVES: To investigate the association of growth hormone (GH) and insulin-like growth factor (IGF-1) burden with the cardiac structural and functional changes in acromegaly patients. METHODS: Ninety-nine acromegaly patients were enrolled in this study. According to the normal range of echocardiographic parameters of Peking Union Medical College Hospital, the patients were divided into parameter normal group and abnormal group. Correlation analyses were conducted between duration of disease, mean GH, mean IGF-1, GH burden, IGF-1 burden and echocardiography data retrospectively. RESULTS: Forty eight cases (48.5%) was diagnosed as abnormal echocardiography, including enlargement of the cardiac cambers (29.3%), valvular diseases (15.1%), dilation of aortic root (5.1%), functional abnormal of left ventricle (19.2%) and wall motion abnormalities (1.0%). The average GH and IGF-1 burdens in echocardiography abnormal group (n=48) were higher than those in the normal group (n=51), without statistical significant except for the left ventricle end-systolic diameter (LVESD) (P=0.018) in GH burden comparison and E/A (P=0.011) and left atrium longitudinal dimension (LALD) (P=0.017) in IGF-1 burden comparison. Abnormal diastolic function group (n=18) had similar GH burden with the normal group (n=81) (P=0.419), but had higher IGF-1 burden than the normal group did (P=0.018).The GH burden correlated with left ventricle end-diastolic diameter (LVEDD) and LVESD, and the IGF-1 burden correlated with left ventricular ejection fraction (LVEF) , LALD, right ventricle longitudinal dimension( RVLD), Left ventricular posterior wall thickness (LVPWT), LVEDD, LVESD, and E/A ratio statistical significantlly (P<0.05). CONCLUSIONS: There exist associations of GH and IGF-1 burden with echocardiography abnormalities and cardiac complications.

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

Application of Preoperative CT/MRI Image Fusion in Target Positioning for Deep Brain Stimulation.

Objective To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.Methods We retrospectively analyzed the clinical data and images of 79 cases (68 with Parkinson's disease, 11 with dystonia) who received preoperative CT/MRI image fusion in target positioning of subthalamic nucleus in deep brain stimulation. Deviation of implanted electrodes from the target nucleus of each patient were measured. Neurological evaluations of each patient before and after the treatment were performed and compared. Complications of the positioning and treatment were recorded.Results The mean deviations of the electrodes implanted on X, Y, and Z axis were 0.5 mm, 0.6 mm, and 0.6 mm, respectively. Postoperative neurologic evaluations scores of unified Parkinson's disease rating scale (UPDRS) for Parkinson's disease and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) for dystonia patients improved significantly compared to the preoperative scores (P<0.001); Complications occurred in 10.1% (8/79) patients, and main side effects were dysarthria and diplopia.Conclusion Target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation has high accuracy and good clinical outcomes.

[Molecular Biological Roles of Oxidative Stress in Acute Brain Ischemia].

The pathogenesis of acute brain ischemia is very complex, involving multiple mechanisms including excessive free radical generation. Oxidative stress means the imbalance between the generation and removal of free radicals. Once acute brain ischemia occurs, the reactive oxygen species interact with large numbers of biomacromolecules, irreversibly change or destroy the functions of cellular lipids, proteins, and nucleic acids, and thus initiate cell signaling pathways. However, the molecular biological characteristics of oxidative stress and the way to prevent and treat acute brain ischemia still need further investigations.

Effect of Transsphenoidal Adenectomy on Glucose Tolerance Status in Patients with Growth Hormone-secreting Pituitary Adenoma.

OBJECTIVE: To explore the effect of transsphenoidal adenectomy on glucose tolerance status in patients with growth hormone (GH)-secreting pituitary adenoma. METHODS: The clinical data of 105 patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenectomy in our department in 2013 were retrospectively analyzed. The glucose tolerance status, GH level, and insulin-like growth factor-1 (IGF-1) level before and after surgery were compared. RESULTS: Among these 105 patients, the blood glucose tolerance status included normal glucose tolerance (NGT) in 47 cases (44.8%), early carbohydrate metabolism disorders (ECMDs) in 26 cases (24.8%), and diabetes mellitus (DM) in 32 cases (30.5%) before surgery. After the surgery, the fasting blood glucose (P=0.006, P=0.017) and postprandial blood glucose (P=0.000, P=0.000) in the ECMDs and DM groups were significantly improved. Also, the random GH (P=0.001, P=0.004, P=0.001), nadir GH (P=0.000, P=0.001, P=0.001), and IGF-1 (P=0.005, P=0.000, P=0.000) significantly decreased during the follow-up period in NGT, ECMDs and DM groups. Compared with ECMDs and DM groups, the decrease in fasting blood glucose (P=0.029, P=0.000), postprandial blood glucose (P=0.003, P=0.000), and serum IGF-1 (P=0.048, P=0.000) were more significant in DM group. CONCLUSIONS: Transsphenoidal adenectomy can improve the blood glucose, GH, and IGF-1 levels in patients with growth hormone-secreting pituitary adenoma. Meanwhile,the surgery has a better effect in improving the glucose tolerance status and IGF-1 in patients with preoperatively confirmed DM.

Predictive Factor of Surgical Efficacy in Male Patients with Prolactinoma.

Objective To analyze the predictive factor of surgical efficacy in male patients with prolactinoma. Method The clinical data of 184 male patients with prolactinoma who had undergone surgery were retrospectively analyzed.Results Before the surgery,the serum prolactin level from 150 to 204 952 ng/ml,the tumors sized 6 to 70 mm. Macroadenoma was seen in 152 cases (82.6%) and suprasellar adenoma with visual deficitsin 75 cases (40.7%). Complete resection was achieved in 149 patients. After surgical therapy,postoperative immediate prolactin level declined in 182 patients (98.4%);57 patients (31.0%)achieved initial remission,while the disease recurred in 26 patients (45.6%).Larger tumor had significantly lower rate of complete resection (P<0.05). The recurrence rate was significantly higher in the group with higher Ki-67 index (P<0.001). The recurrence rate was significantly lower in patients with intrasellar adenoma (P<0.001).No significant relationship was found between preoperative prolactin level and complete resection (P=0.306). Conclusions Tumor size can predictthe degree of surgical resection. The prognostic factors include tumor size,preoperative growth pattern of prolactinoma,and Ki-67 index.

Protection of Nerve Injury with Exosome Extracted from Mesenchymal Stem Cell.

OBJECTIVE: To investigate the protective effect of Exosomes from human adipose-derived mesenchymal stem cells (hAMSCs) in neural injury induced by glutamate and its possible mechanism. METHODS: Characteristics of Exosomes from hAMSCs were identified by electron microscopy and Western blot analysis. Cytokines that might play a major role in the protective effect were tested by enzyme-linked immunosorbent assay (ELISA). The protective action of Exosome and its possible signaling pathway were researched by the in vitro neural injury induced by glutamate, including control group (without Glu), Glu group (dealing with Glu), Glu+Exo group (dealing with Glu +100 ng/ml Exo), Glu+Exo+Akt group (dealing with Glu+100 ng/ml Exo+10 µmol/L Akt), Glu+Exo+Erk group (dealing with 100 ng/ml Glu+100 ng/ml Exo+10 µmol/L Erk), and Glu+Exo+TrkB group (dealing with Glu+100 ng/ml Exo +10 µmol/L TrkB). RESULTS: Exosomes from hAMSCs had similar sizes to those isolated from other kinds of cells, and expressed the characteristic proteins such as CD63, CD81, HSP70, and HSP90. Cytokines that had neurotrophic effects on Exosomes were mainly insulin-like growth factor and hepatocyte growth factor, with the concentration being 9336.49±258.63 and 58,645.50±16,014.62, respectively; brain derived neurotrophic factor, nerve growth factor,and vascular endothelial growth factor had lower levels, with the concentration being 1928.25±385.47, 1136.94±5.99, and 33.34±9.43, respectively. MTS assay showed that the PC12 cell survival rates were 0.842±0.047, 0.306±0.024, 0.566±0.026, 0.461±0.016, 0.497±0.003, and 0.515±0.034 in the control group, Glu group, Glu+Exo group, Glu+Exo+Akt group, Glu+Exo+Erk group, and Glu+Exo+TrkB group; obviously, it was significantly lower in Glu group than in control group (P=0.02), significantly higher in Glu+Exo group than in Glu group (P=0.01), and significantly lower in Glu+Exo+Akt group than in Glu+Exo group (P=0.01). CONCLUSION: Exosomes secreted from hAMSCs have protective effect against neuron damage induced by glutamate, which may be mediated through activating the PI3/K-Akt signalling pathway.

Potential of neural stem cell-based therapies for Alzheimer's disease.

Alzheimer's disease (AD), known to be a leading cause of dementia that causes heavy social and financial burdens worldwide, is characterized by progressive loss of neurons and synaptic connectivity after depositions of amyloid-ß (Aß) protein. Current therapies for AD patients can only alleviate symptoms but cannot deter the neural degeneration, thus providing no long-term recovery. Neural stem cells (NSCs), capable of self-renewal and of differentiation into functional neurons and glia, have been shown to repair damaged networks and reverse memory and learning deficits in animal studies, providing new hope for curing AD patients by cell transplantation. Under AD pathology, the microenvironment also undergoes great alterations that affect the propagation of NSCs and subsequent therapeutic efficiency, calling for measures to improve the hostile environment for cell transplantation. This article reviews the therapeutic potential of both endogenous and exogenous NSCs in the treatment of AD and the challenges to application of stem cells in AD treatment, particularly those from the microenvironmental alterations, in the hope of providing more information for future research in exploiting stem cell-based therapies for AD. © 2015 Wiley Periodicals, Inc.

Transplantation of Human Neural Stem Cells in a Parkinsonian Model Exerts Neuroprotection via Regulation of the Host Microenvironment.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons and consequent dopamine (DA) deficit, and current treatment still remains a challenge. Although neural stem cells (NSCs) have been evaluated as appealing graft sources, mechanisms underlying the beneficial phenomena are not well understood. Here, we investigate whether human NSCs (hNSCs) transplantation could provide neuroprotection against DA depletion by recruiting endogenous cells to establish a favorable niche. Adult mice subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were transplanted with hNSCs or vehicle into the striatum. Behavioral and histological analyses demonstrated significant neurorescue response observed in hNSCs-treated animals compared with the control mice. In transplanted animals, grafted cells survived, proliferated, and migrated within the astrocytic scaffold. Notably, more local astrocytes underwent de-differentiation, acquiring the properties of NSCs or neural precursor cells (NPCs) in mice given hNSCs. Additionally, we also detected significantly higher expression of host-derived growth factors in hNSCs-transplanted mice compared with the control animals, together with inhibition of local microglia and proinflammatory cytokines. Overall, our results indicate that hNSCs transplantation exerts neuroprotection in MPTP-insulted mice via regulating the host niche. Harnessing synergistic interaction between the grafts and host cells may help optimize cell-based therapies for PD.

[Correlation between Expression of Signal Transducer and Activator of Transcription 3 and Pituitary Adenoma Subtypes].

OBJECTIVE: To investigate the correlation between signal transducer and activator of transcription 3 (STAT3) expression and pituitary adenoma subtypes. METHOD: The STAT3 expression profiles in different pituitary adenomas from 74 patients were determined using quantificational real-time polymerase chain reaction,Western blot,and immunohistochemistry. RESULTS: Expression of STAT3 was observed in all pituitary adenoma subtypes. The STAT3 expression level was highest in growth hormone adenoma when compared with other tumors including prolactin,follicle-stimulating hormone/luteinizing hormone-secreting adenoma,and adrenocorticotrophic hormone-secreting adenoma. The follicle-stimulating hormone/luteinizing hormone adenomas exhibited the lowest STAT3 expression levels. CONCLUSION: STAT3 is differentially expressed in pituitary adenoma subtypes, suggesting the cell-specific features of STAT3 regulation,although further investigations are still warranted to clarify the underlying mechanisms.

[Diagnosis and Treatment of Pituitary Carcinoma].

The early diagnosis and treatment of pituitary carcinoma is difficult. The diagnosis is often delayed, and the confirmation of a diagnosis requires the presence of distant subarachnoid,brain or systemic metastasis from the primary pituitary tumor in the sella and also needs the evidences of pathology and imaging of the primary pituitary carcinoma and metastases. Treatment of pituitary carcinoma includes surgery, radiation therapy ,hormone therapy, chemotherapy, and molecularly targeted therapy; however, these methods are mainly palliative and can not prolong the survival. The prognosis remains poor. Efforts should be made to develop more effective diagnosis and treatment options.

Probiotics' preventive effect on pediatric food allergy: a meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the preventive effect of probiotics on pediatric food allergy. METHODS: From MEDLINE bibliographical database, we searched and reviewed all randomized controlled trials on the preventive effects of probiotics on pediatric food allergies up to September 2013 and excluded the studies that do not meet inclusion criteria and extracted the data. Meta-analysis for the results of homogenous studies was performed using RevMan 5.0 and the co-effect was pooled by using fixed-effects model of relative risk (RR) ratios. RESULTS: Ten trials published between 2007 and 2012 including 2701 cases were included. Meta-analysis based on included data showed that the preventive effect of prenatal and postnatal probiotic supplementation on food allergies was not significant with the RR=0.88 (95% CI: 0.76-1.03). CONCLUSION: Present evidences cannot show in unequivocal terms that prenatal and postnatal probiotic supplementation will prevent food allergic diseases.

Role of p66Shc gene in human longevity.

The p66Shc gene has emerged as a novel gerontogene affecting health and life during aging. In murine models of aging,a genetic deficiency of the p66Shc gene,which encodes a phosphotyrosine signal adapter protein,extends life span by 30%. p66Shc is a crucial regulator of reactive oxygen species levels and is involved in age-related dysfunctions. UP to now,oxidative stress has been recognized to be involved in human diseases such as high cholesterol,diabetes,and cardiovascular diseases. Further study on the role of p66Shc will facilitate the research of novel disease-targetted drugs and slow down or cure age-related pathologies.

Research advances in the application of methylprednisolone in the treatment of acute spinal cord injury.

Acute spinal cord injury(ASCI),mainly caused by traffic accidents and fall injuries,is a catastrophic event that can profoundly affect the trajectory of a patient's life. Debate continues over the medical management of ASCI,in particular the usefulness,dosage,and potential risks of methylprednisolone(MP). Although the results of American National Acute Spinal Cord Injury Study 2 and 3 trials led to the wide adoption of a high-dose MP regimen for ASCI patients,the reliabilities of their study methods and data were still questionable. Based on the currently available literature,we conclude that high-dose MP is no longer a recommended therapy for ASCI;however,due to the lack of effective treatment,it remains a useful option for this condition.

[Treatment of pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques].

OBJECTIVE: To study the effectiveness of treating giant pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques. METHODS: A total of 72 patients who underwent neuroendoscopic surgery and 55 patients who underwent microscopic surgery for giant pituitary adenomas were enrolled in this retrospective analysis. Both groups received expanded endoscopic endonasal transsphenoidal approach, intraoperative application of navigation, and Doppler.The clinical data of two groups were compared. RESULTS: The two groups were significantly different in total tumor removal rate, operation time, postoperative nasal patency, and postoperative recurrence rate (P=0.004, P=0.0003, P=0.000, and P=0.002, respectively), whereas the cerebrospinal fluid leakage, postoperative diabetes insipidus, and cranial nerve injury were not significantly different (P > 0.05). CONCLUSIONS: Expanded neuroendoscopic endonasal transsphenoidal approach assisted by multiple techniques is the preferred surgical method for giant invasive pituitary adenomas invading cavernous sinus.The lateral cavernous sinus approach and the further molecular biology research will bring more options for the treatment of invasive pituitary adenomas.

Stereotactically intracerebral transplantation of neural stem cells for ischemic stroke attenuated inflammatory responses and promoted neurogenesis: an experimental study with monkeys.

BACKGROUND: Ischemic stroke is a common neurovascular disorder with high morbidity and mortality. However, the underlying mechanism of stereotactically intracerebral transplantation of human neural stem cell (hNSC) is not well elucidated. MATERIALS AND METHODS: Four days after ischemic stroke induced by Rose Bengal photo-thrombosis, 7 cynomolgus monkeys were transplanted with hNSCs or vehicles stereotactically and followed up for 84 days. Behavioral assessments, magnetic resonance imaging, blood tests, and pathological analysis were performed before and after treatment. The proteome profiles of the left and right precentral gyrus and hippocampus were evaluated. Extracellular vesicle micro-RNA (miRNA) from the peripheral blood was extracted and analyzed. RESULTS: hNSC transplantation reduced the remaining infarcted lesion volume of cynomolgus monkeys with ischemic stroke without remarkable side effects. Proteomic analyses indicated that hNSC transplantation promoted GABAergic and glutamatergic neurogenesis, and restored the mitochondrial electron transport chain function in the ischemic infarcted left precentral gyrus or hippocampus. Immunohistochemical staining and qRT-PCT confirmed the promoting effects on neurogenesis and revealed that hNSCs attenuated post-infarct inflammatory responses by suppressing resident glia activation and mediating peripheral immune cell infiltration. Consistently, miRNA-sequencing revealed the miRNAs which were related to these pathways were down-regulated after hNSC transplantation. CONCLUSIONS: This study indicates that hNSCs can be effectively and safely used to treat ischemic stroke by promoting neurogenesis, regulating post-infarct inflammatory responses, and restoring mitochondrial function in both the infarct region and hippocampus.

Pairwise machine learning-based automatic diagnostic platform utilizing CT images and clinical information for predicting radiotherapy locoregional recurrence in elderly esophageal cancer patients.

OBJECTIVE: To investigate the feasibility and accuracy of predicting locoregional recurrence (LR) in elderly patients with esophageal squamous cell cancer (ESCC) who underwent radical radiotherapy using a pairwise machine learning algorithm. METHODS: The 130 datasets enrolled were randomly divided into a training set and a testing set in a 7:3 ratio. Clinical factors were included and radiomics features were extracted from pretreatment CT scans using pyradiomics-based software, and a pairwise naive Bayes (NB) model was developed. The performance of the model was evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). To facilitate practical application, we attempted to construct an automated esophageal cancer diagnosis system based on trained models. RESULTS: To the follow-up date, 64 patients (49.23%) had experienced LR. Ten radiomics features and two clinical factors were selected for modeling. The model demonstrated good prediction performance, with area under the ROC curve of 0.903 (0.829-0.958) for the training cohort and 0.944 (0.849-1.000) for the testing cohort. The corresponding accuracies were 0.852 and 0.914, respectively. Calibration curves showed good agreement, and DCA curve confirmed the clinical validity of the model. The model accurately predicted LR in elderly patients, with a positive predictive value of 85.71% for the testing cohort. CONCLUSIONS: The pairwise NB model, based on pre-treatment enhanced chest CT-based radiomics and clinical factors, can accurately predict LR in elderly patients with ESCC. The esophageal cancer automated diagnostic system embedded with the pairwise NB model holds significant potential for application in clinical practice.

Study on the expression levels of CXCR4, CXCL12, CD44, and CD147 and their potential correlation with invasive behaviors of pituitary adenomas.

OBJECTIVE: To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. METHODS: Fresh pituitary adenoma specimens were collected from 35 pituitary adenoma (21 invasive and 14 non-invasive) patients who underwent surgical treatment in our Neurosurgery Department between January and April of 2009. The expression levels of CXCR4, CXCL12, CD44, and CD147 were evaluated firstly by flow cytometry, fluorescence microscopy in single cell suspensions, and then by immunohistochemical staining of paraffin tissue sections. RESULTS: Flow cytometric analyses showed that the percentage of CXCR4- and CXCL12-positive cells from invasive pituitary adenomas (IPA) was significantly higher in the single cell suspensions than that from non-invasive pituitary adenomas (nIPA) (P<0.05). Immunohistochemical staining revealed that CXCR4 and CXCL12 staining index scores of the invasive pituitary adenomas were significantly higher than those of the non-invasive pituitary adenomas (P<0.05). In contrast, neither flow cytometry nor immunohistochemical staining demonstrated significant difference between CD44 and CD147 expression levels, respectively. CONCLUSION: Expression levels of CXCR4 and CXCL12 are correlated with the invasiveness of pituitary adenomas. Therefore, rather than CD44 and CD147, CXCR4 and CXCL12 may potentially serve as biomarkers for early detection of pituitary adenomas.