Suojun Zhang

Downregulation of LRIG1 expression by RNA interference promotes the aggressive properties of glioma cells via EGFR/Akt/c-Myc activation

The LRIG1 [leucine-rich repeats and immunoglobulin-like domains (LRIG)] gene is not universally downregulated in human cancers, and its role in tumorigenesis and the development of glioma has not been well addressed. In this study, we used short hairpin RNA (shRNA)-triggered RNA interference (RNAi) to block LRIG1 gene expression in the GL15 human glioma cell line. Specific downregulation of LRIG1 by shRNA resulted in significantly enhanced capabilities of proliferation, inhibition of apoptosis and invasion in the GL15 cells. LRIG1 repression induced marked activation of epidermal growth factor receptor (EGFR), protein kinase B (Akt) and c-Myc signaling molecules. Our results demonstrated that RNAi against LRIG1 may effectively downregulate LRIG1 gene expression. LRIG1 functions as a tumor suppressor in the pathogenesis of glioma via EGFR/Akt/c-Myc activation.

Identification of U251 glioma stem cells and their heterogeneous stem‑like phenotypes

Glioblastoma, the most common and lethal type of intracranial tumor, is characterized by extensive heterogeneity at the cellular and molecular levels. The discovery of glioma stem cells (GSCs) lends support to a new paradigm in tumor biology. In the present study, we aimed to clarify the validity of using U251 glioma cells as a source of GSC culture and critically evaluate the heterogeneous stem-like phenotypes of these cells when grown under various culture conditions. The findings suggested that U251 cells (U251-Adh, U251-SC-Sph and U251-SC-Adh) showed distinctive growth patterns and self-renewal capacity. The U251 glioma cell line is endowed with certain GSC phenotypes that may be moderately enriched in vitro when transferred into stem cell culture conditions, although this is not sustainable and reproducible in vivo. Notably, glioma cells are plastic in response to their environment. The reversible adaptive plasticity contributes to the GSC heterogeneity, which may lead to the heterogeneity of glioblastoma and the differing responses to current therapies. Therefore, an improved understanding of GSC heterogeneity is urgently required for designing more effective therapies against this highly malignant brain tumor.

Surgical treatment of cerebellar schistosomiasis.

OBJECTIVETo explore the surgical treatment of cerebellar schistosomiasis. METHODSTwelve cases of cerebellar schistosomiasis treated in our department were analyzed retrospectively. RESULTSAll cases were cured. At the 2-year follow-up examination, all patients could perform physical tasks normally. CONCLUSIONCerebellar schistosomiasis tends to cause mass effect of the posterior cranial fossa and increased intracranial pressure. Microresection of the pathological focus and decompression of the posterior cranial fossa should be effective therapeutic measures.

Neural stem cells preferentially migrate to glioma stem cells and reduce their stemness phenotypes.

Glioma stem cells (GSCs), characterized by self-renewal, multi-potentiality and tumorigenicity, are responsible for the tumor propagation, recurrence and resistance to traditional treatments, representing a critical therapeutic target. Neural stem cells (NSCs) possess inherent tropism to brain tumor cells and inhibit their growth. However, there is a limited understanding of the mechanism underlying NSC tropism and the effect of NSC migration on GSC stemness phenotypes. In the present study, we showed that GSCs exhibited enhanced chemotaxis for NSC tropism compared with their differentiated cells. Chemokines secreted by GSCs contributed to the targeted migration of NSCs. Hypoxia enhanced NSC tropism via the upregulated chemokine expression of GSCs, such as VEGF, EGF and bFGF. In vitro migration of NSCs induced GSC differentiation and reduced stem-like phenotypes. Moreover, in vivo data provided direct evidence that transplanted NSCs could migrate to GSCs from either the homolateral or contralateral brain injection site, which prolonged the survival of grafted mice. Taken together, these findings show that NSCs preferentially migrate to GSCs and reduce their stemness phenotypes, raising the intriguing possibility that the targeted migration of NSCs can be applied as a novel therapeutic strategy to target these intractable brain tumors.

Diagnosis and treatment of clear cell hidradenocarcinoma of the scalp

SummaryClear cell hidradenocarcinoma (CCH) is an exceedingly rare and highly malignant tumor of the eccrine sweat glands. Its treatment is extremely difficult due to the characteristically aggressive clinical course including repeated local recurrence and uncontrollable distal metastasis coming along with a very poor prognosis. Most published case studies recommend a wide surgical excision followed by adjuvant conservative therapy, which is generally considered to be the standard treatment. Two cases of nodular CCH of the scalp either presenting as a singular primary lesion or at an already metastatic stage were analyzed retrospectively. Wide local excision of the tumor couldn’t prevent the primary carcinoma from recurring and metastasizing. Both cases received various therapies but the results were unsatisfactory. Although most authors have recommended that early wide surgical excision of the tumor is a feasible therapeutic measurement, our results raise doubts on the efficacy of this treatment strategy. As alternative approaches (i.e. chemotherapy, radiotherapy) are similarly controversial, further studies and a wide exchange of clinical experiences are crucial.

The protective effect of propofol on erythrocytes during cardiopulmonary bypass

SummaryTo evaluate the relationship between erythrocyte injury and intracellular calcium ion overload, and the protective effect of propofol on erythrocytes during cardiopulmonary bypass (CPB). 40 children with congenital heart diseases who underwent surgical repair under CPB were included. The patients were randomly divided into two groups: control group (group C) and propofol group (group P). Anesthesia was maintained in the patients with 6 mg/kg/h propofol in Group P, and those in the Group C inhaled 1%–2% isoflurane. The blood samples were taken before CPB, 30 min after CPB, at the end of CPB, and 2 h and 24 h after CPB to measure the content of erythrocyte intracellular calcium ion (E−Ca2+), Ca2+−Mg2+-ATPase and Na+−K+-ATPase activities, index filtration of erythrocytes (IF), mean corpuscular volume (MCV) and the concentration of plasma free hemoglobin (F−Hb). Results showed that in the control group, E−Ca2+, IF, MCV and F−Hb were gradually increased and Ca2+−Mg2+-ATPase and Na+−K+-ATPase activities were decreased. The increase of E−Ca2+ was linearly paralleled to IF, MCV and F−Hb. In propofol group, all the above-mentioned parameters were significantly improved (P<0.05). This study suggests that erythrocyte injury is related to elevation of intracellular calcium during CPB and propofol has a protective effect on erythrocyte injury.

Label-retaining assay enriches tumor-initiating cells in glioblastoma spheres cultivated in serum-free medium.

Label-retaining cells, which are characterized by dormancy or slow cycling, may be identified in a number of human normal and cancer tissues, and these cells demonstrate stem cell potential. In glioblastoma, label-retaining assays to enrich glioma stem cells remain to be fully investigated. In the present study, glioblastoma sphere cells cultured in serum-free medium were initially stained with the cell membrane fluorescent marker DiI. The fluorescence intensity during cell proliferation and sphere reformation was observed. At 2 weeks, the DiI-retaining cells were screened by fluorescence-activated cell sorting and compared phenotypically with the DiI-negative cells in terms of in vitro proliferation, clonogenicity and multipotency and for in vivo tumorigenicity, as well as sensitivity to irradiation and temozolomide treatment. It was observed that DiI-retaining cells accounted for a small proportion, <10%, within the glioblastoma spheres and that DiI-retaining cells proliferated significantly more slowly compared with DiI-negative cells (P=0.011, P=0.035 and P=0.023 in the of NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines). Significantly increased clonogenicity (P=0.002, P=0.034 and P=0.016 in the NCH441, NCH644 and NCH421k glioblastoma sphere cell lines) and three-lineage multipotency were observed in DiI-retaining cells in vitro compared with DiI-negative cells. As few as 100 DiI-retaining cells were able to effectively generate tumors in the immunocompromised mouse brain, whereas the same number of DiI-negative cells possessed no such ability, indicating the increased tumorigenicity of DiI-retaining cells compared with DiI-negative cells. Furthermore, DiI-retaining cells demonstrated significant resistance following irradiation (P=0.012, P=0.024 and P=0.036) and temozolomide (P=0.003, P=0.005 and P=0.029) compared with DiI-negative cells in the NCH421k, NCH441 and NCH644 glioblastoma sphere cell lines, respectively. It was concluded that label-retaining cells in glioblastoma spheres manifest clear stem cell features and that the label-retaining assay may be utilized to further enrich glioma stem cells cultured under serum-free conditions for additional study.

Clinical evaluation of post-operative cerebral infarction in traumatic epidural haematoma

ABSTRACT Background: Patients with traumatic epidural haematoma, undergoing the prompt and correct treatment, usually have favourable outcomes. However, secondary cerebral infarction may be life-threatening condition, as it is difficult to be identified before neurological impairment occurs. Objective: To evaluate the clinical data of patients with traumatic EDH and assess potential risk factors for post-operative cerebral infarction. Methods: The clinical data of patients with traumatic EDH were collected and analysed retrospectively. Results: The univariate analysis revealed 10 potential risk factors (the haematoma location, volume, the largest thickness and mid-line shift, basal cisterns compression, traumatic subarachnoid haemorrhage, pupil dilatation, pre-operative Glasgow Coma Scale score, ∆GCS and intraoperative brain pressure) for cerebral infarction with statistically significant difference. Of these factors, haematoma volume and basal cistern compression turned out to be the most significant risk factors through final multivariate logistic regression analysis. Conclusion: The findings of this study can provide predictive factors for development of cerebral infarction and information for clinical decision-making and future studies.