MiR-218-5p targets LHFPL3 to regulate proliferation, migration, and epithelial-mesenchymal transitions of human glioma cells.

Glioblastoma (GBM) is a main subtype of high-grade gliomas with features in progressive brain tumor. Lipoma HMGIC fusion partner-like 3 (LHFPL3) is reported to be highly expressed in malignant glioma, but the relationship and mechanism between LHFPL3 and tumor is inexplicit. The present study aimed to screen the miRNAs targeting LHFPL3 and verify the pathogenesis and development of gliomas. Bioinformatics software predicted that miR-218-5p and miR-138-5p can specifically bind to LHFPL3 mRNA. And the expression of miR-218-5p and miR-138-5p was down-regulated in glioma cell lines and glioma tissues from the patients compared with the normal cells. While dual luciferase activity experiment confirmed, only miR-218-5p can directly bind to LHFPL3. After miR-218-5p transfection of U251 and U87 cells, cytological examinations found a reduction in cell activity, proliferation and invasive ability. Further study showed that miR-218-5p transfection could inhibit epithelial-mesenchymal transitions (EMT). Therefore, miR-218-5p targeting LHFPL3 mRNA plays significant roles in preventing the invasiveness of glioma cells. The present study also revealed a novel mechanism for miRNA-LHFPL3 interaction in glioma cells, which may be potential targets for developing therapies in treating glioma.

Functional Changes of Dendritic Cells in C6 Glioma-Bearing Rats That Underwent Combined Argon-Helium Cryotherapy and IL-12 Treatment.

OBJECTIVE: The aim of this study was to explore changes in tumor tissues of glioma-bearing rats that underwent argon-helium cryoablation as well as changes in antitumor immunity before and after combined interleukin 12 treatment. METHODS: Two hundred sixty Wistar rats were randomly divided into a blank control group, intravenous injection interleukin-12 group, cryotherapy group, and cryotherapy + intravenous injection group. C6 glioma cells proliferated in vitro were implanted subcutaneously on the backs of rats to establish C6 glioma-bearing animal models. Each group underwent the corresponding treatments, and morphological changes in tumor tissues were examined using hematoxylin-eosin staining. CD11c staining was examined using immunohistochemistry, and differences in dendritic cells and T-cell subsets before and after treatment were analyzed using flow cytometry. RESULTS: The control group showed no statistical changes in terms of tumor tissue morphology and cellular immunity, cryotherapy group, and cryotherapy + intravenous injection group, among which the count for the cryotherapy + intravenous injection group was significantly higher than those of all other groups. In the argon-helium cryotherapy group, tumor cells were damaged and dendritic cell markers were positive. The number of CD11c+ and CD86+ cells increased significantly after the operation as did the cytokine interferon-γ level (P < .01), suggesting a shift toward Th1-type immunity. CONCLUSION: Combined treatment of argon-helium cryoablation and interleukin 12 for gliomas not only effectively injured tumor tissues but also boosted immune function and increased antitumor ability. Therefore, this approach is a promising treatment measure for brain gliomas.

In situ dendritic cell vaccination for the treatment of glioma and literature review.

Glioma is one of the greatest threats to human health, and invasive growth of glioma is its major cause of death. Inhibiting or blocking angiogenesis can effectively inhibit tumor growth and metastasis or dramatically reduce the size of the original lesion. Therefore, anti-angiogenic therapy has currently become the most promising treatment strategy for glioma. Although dendritic cells (DCs) used in DC-based immunotherapy are loaded with tumor-associated antigens, the anti-tumor immune response is effectively stimulated in cytotoxic specific T lymphocytes (CTLs), thereby achieving targeted killing of tumor cells without harming surrounding normal cells. This makes it a highly promising new form of therapy. This article reviews the existing evidence regarding in situ DC vaccination for the treatment of glioma and puts forward hypotheses regarding patient, tumor, and technical factors and warrant further investigation.

Associations between SOX2 and miR-200b expression with the clinicopathological characteristics and prognosis of patients with glioma.

The aim of the present study was to investigate the associations between microRNA (miR)-200b and sex determining region Y-box 2 (SOX2) expression with gender, age, clinical staging and pathological staging in 123 patients with glioma. The results revealed higher miR-200b expression levels in the glioma tissue than in the normal brain tissues, and a reduction in miR-200b expression with increasing pathological grading of the gliomas. Immunohistochemistry revealed a 53.7% gross expression rate of SOX2 in the glioma tissues. SOX2 and miR-200b expression levels were significantly correlated with the histological grading of the gliomas (P<0.05); however, no associations were observed with patient gender, age, pathological classification or clinical staging of the glioma (P>0.05). In patients with grade I and II gliomas, no correlation was detected between miR-200b and SOX2, while a significant correlation was observed in grade III and IV gliomas. A median 52-month follow-up revealed 1-, 3- and 5-year gross survival rates of 82.1, 50.0 and 30.7%, respectively, in the 123 patients with a glioma. Univariate analysis revealed no association between survival rate and patient age, gender, Karnofsky Performance Scale score, histological grading or clinical staging (P>0.05). However, miR-200b and SOX2 were independent prognostic factors for glioma (P<0.05). Patients with positive SOX2 expression exhibited a significantly reduced 5-year survival rate, compared with those with negative SOX2 expression (P<0.001). Furthermore, a significantly higher 5-year survival rate was observed in patients with high miR-200b expression than those with low miR-200b expression (P<0.001). The results indicated that SOX2 and miR-200b expression levels are associated with the histological grading of gliomas, but do not correlate with patient gender or age, or the pathological classification or clinical staging of the gliomas. Thus, miR-200b and SOX2 offer useful independent prognostic factors for glioma.

Treatment of Dutch rat models of glioma using EphrinA1-PE38/GM-CSF chitosan nanoparticles by in situ activation of dendritic cells.

Although dendritic cells (DCs) used in DC-based immunotherapy are loaded with tumor-associated antigens, the antitumor immune response is effectively stimulated in cytotoxic specific T lymphocytes (CTLs), thereby achieving targeted killing of tumor cells without harming surrounding normal cells. This makes it a highly promising new form of therapy. In this study, we successfully created chitosan-coated EphrinA1-PE38/GM-CSF nanoparticles and transplanted them into tumor-bearing rats, resulting in the effective killing of glioma tissue and a prolonged life span. Further immunohistochemistry and flow cytometry studies revealed that the treatment was effective in increasing the number of dendritic cell activations under an immunomodulatory response. These results suggest that chitosan-coated EphrinA1-PE38/GM-CSF nanoparticles may be effective in inducing in situ activation of DCs in glioma-bearing rats, thereby generating DC vaccines in vivo.

A novel recombinant protein of ephrinA1-PE38/GM-CSF activate dendritic cells vaccine in rats with glioma.

Dendritic cells loaded with tumor-associated antigens can effectively stimulate the antitumor immune response of cytotoxic T lymphocytes in the body, which facilitates the development of novel and effective treatments for cancer. In this study, the adenovirus-mediated ephrinA1-PE38/GM-CSF was successfully constructed using the overlap extension method, and verified with sequencing analysis. HEK293 cells were infected with the adenovirus and the cellular expression of ephrinA1-PE38/GM-CSF was measured with an enzyme-linked immunosorbent assay. The recombinant adenovirus was then delivered into the tumor-bearing rats and the results showed that such treatment significantly reduced the volumes of gliomas and improved the survival of the transplanted rats. The results from immunohistochemistry and flow cytometry suggested that this immunomodulatory agent cause activation of dendritic cells. The findings that ephrinA1-PE38/GM-CSF had a high efficacy in the activation of the dendritic cells would facilitate the development of in vivo dendritic-cell vaccines for the treatment of gliomas in rats. Our new method of DC vaccine production induces not only a specific local antitumor immune response but also a systemic immunotherapeutic effect. In addition, this method completely circumvents the risk of contamination related to the in vitro culture of DCs, thus greatly improving the safety and feasibility of clinical application of the DC vaccines in glioma.

[Individual surgical treatment of craniocervical junction malformation].

OBJECTIVE: To explore the individual surgical treatment of various performance types of craniocervical junction malformation. METHODS: From January 2011 to December 2013, 112 patients with craniocervical junction malformations were treated at our department, including Chiari malformation (n = 65) (syringomyelia, n = 58 and without syringomyelia, n = 7), basilar invagination disease (n = 35) (with cerebellar tonsillar herniation malformation or occipitocervical fusion) and complex craniocervical malformation (n = 22) (atlantoaxial dislocation with occipitocervical fusion or with chiari malformation or cervical insufficiency sub-section). All of them had the symptoms of upper cervical nerve damage. For those with Chiari malformation, we evaluated atlanto-occipital joint stability preoperatively. If atlanto-occipital joint was stable, we performed small occipital bone window decompression, partial removal of cerebellar tonsils, loosening of posterior fossa, upper cervical adhesions, artificial dura appropriate sutured dural repair expanding neck pillow. For patients with basilar invagination, if nerve compression performance was in the rear, posterior decompression was performed. For those with complex craniocervical malformation with atlantoaxial dislocation, neck traction under anesthesia or traction after anterior release, then pillow neck fixation and fusion were performed. RESULTS: During follow-ups, the symptoms improved significantly (n = 98, 87.51%). There were no symptomatic change (n = 10, 8.93%), postoperative neurological deterioration (n = 3, 2.67%) and death (n = 1, 0.89%). CONCLUSION: According to specific clinical manifestations of craniocervical junction malformation patients, the best treatment is to perform individualized surgeries after thorough preoperative evaluations.

Lobeline shows protective effects against MPTP-induced dopaminergic neuron death and attenuates behavior deficits in animals.

We previously demonstrated that lobeline effectively inhibited dopamine transporter (DAT)-mediated dopamine (DA) transportation. Therefore, the present study aimed to investigate whether lobeline shows protective effects against neurotoxin-induced cell death in vivo. Mice were administered 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) and treated with 80 mg/kg L-dopa, 10 mg/kg GBR12935 or 1 or 3 mg/kg lobeline, respectively, via injection. Rotarod and swim tests as well as tyrosine hydroxylase (TH) immunohistochemistry were carried out to evaluate the effects of these drugs. Compared with L-DA and GBR12935, lobeline (3 mg/kg administered via intraperitoneal injection) on behavior and dopaminergic neurons. Compared with L-DA and GBR12935, lobeline (3 mg/kg injected subcutaneously) significantly reduced MPTP induced locomotive deficits detected in behavioral tests. In addition, TH immunostaining showed that lobeline (3 mg/kg) markedly decreased the neurotoxin-induced immunoreactivity loss in the substantia nigra and striatum. Lobeline may be useful in the protection of dopaminergic neurons and may alleviate the symptoms of Parkinson's disease.

[Roles of computed tomography in the diagnosis and treatment of complex atlas pillow deformity].

OBJECTIVE: To explore the roles of computed tomography (CT) in the diagnosis and treatment of complex atlas pillow deformity. METHODS: From January 2010 to February 2012, the preoperative and postoperative CT imaging findings were collected from 32 cases of complicated atlas pillow deformity undergoing surgical treatment at Henan Provincial People's Hospital. There were 18 males and 14 females with a mean age of 36.8 years (range: 23 - 65). The average duration of disease was 4.5 years (range: 0.25 - 10). RESULTS: In 32 cases, a definite diagnosis was established preoperatively by coronary sagittal CT scans and 3-dimensional reconstruction. And CT re-examinations were performed to review the postoperative curative efficacies. CONCLUSION: CT imaging examination is of vital importance in the diagnosis, personalized surgical procedures and prognostic evaluation of complex craniocervical junction deformity.

Microvascular decompression for hemifacial spasm: technical notes on pontomedullary sulcus decompression.

BACKGROUND: Hemifacial spasm usually results from compression of facial nerve by offending vessels. During microvascular decompression, offending vessels at pontomedullary sulcus are obscured by the lower cranial nerve roots, making exposure and surgery difficult. This study discusses the techniques for decompression of offending vessels in this area. METHODS: Of 213 patients who underwent microvascular decompression for hemifacial spasm, 34 patients had compression of the facial nerve at the pontomedullary sulcus by offending vessels. Details of the intraoperative exposure and the arrangement of the lower cranial nerve roots are reviewed. The handling of the vertebral artery (VA) and the protection of perforating vessels is also discussed. RESULTS: Sixteen patients had the compact type of cranial nerve root arrangement, 13 had the loose type and five had the solitary type. Fifteen patients had compression by the VA. At 1 year after surgery, 30 patients had excellent results, two had good results and two had poor results. CONCLUSIONS: Microvascular decompression for hemifacial spasm can be performed with satisfying results if there is full exposure and protection of the perforating vessels, appropriate use of the spaces between cranial nerve roots, and attention paid to the characteristics of offending vessels.

[Treatment strategies for complicated craniocervical junction malformations].

OBJECTIVE: To explore the treatment strategies for complicated craniocervical junction malformations with diverse clinical and imaging features. METHODS: The clinical data of 67 cases of complicated craniocervical junction malformation treated between January 2000 to December 2010 were retrospectively analyzed. Based on their clinical manifestations and imaging findings, different operative procedures were adopted, including odontoidectomy via transoral transpharyngeal approach (n = 3), occipito-cervical fusion and(or) suboccipital decompression (n = 19) and odontoidectomy via transoral transpharyngeal approach followed by occipito-cervical fusion in two-stage operation (n = 25). Four cases underwent merely odontoidectomy via transoral transpharyngeal approach and died postoperatively. Sixteen cases had occipito-cervical fusion and(or) transorally surgical release for reduction in one stage. RESULTS: Clinical symptoms significantly improved in 19 cases, partially improved in 21 cases and remained unchanged in 12 cases. Nine cases deteriorated postoperatively and 6 cases died. The effective rate was 59.7%. CONCLUSION: The complexity of craniocervical junction malformations may be fully assessed based on different clinical manifestations and thorough imaging studies. Then personalized operative plans are to be designed.

HOXB7 as a prognostic factor and mediator of colorectal cancer progression.

PURPOSE: This study was to investigate the clinicopathologic significance and potential role of HOXB7 in the development and progression of colorectal cancer (CRC). EXPERIMENTAL DESIGN: The relationship between HOXB7 expression and clinical characteristics of CRC was analyzed in 224 paraffin-embedded archived CRC specimens by immunohistochemistry (IHC). The effects of HOXB7 on cell growth and proliferation, as well as on tumorigenesis, were examined both in vitro and in vivo, using MTT assay, colony formation assay, cell cycle analysis, soft agar assay, and tumorigenesis in nude mice. Western blotting and real-time reverse transcriptase-PCR were performed to examine the impact of HOXB7 on the PI3K/Akt and MAPK signaling pathways. RESULTS: HOXB7 protein level was significantly correlated with advanced Dukes stage (P < 0.001), T stage (P = 0.012), distant metastasis (P = 0.042), higher proliferation index (P = 0.007) and poor survival of patients (P = 0.005). Enforced expression of HOXB7 in CRC cell lines significantly enhanced cell growth, proliferation and tumorigenesis. Conversely, knockdown of HOXB7 caused an inhibition of cell growth, proliferation, and tumorigenesis. We also showed that HOXB7 accelerated G(0)-G(1) to S-phase transition concomitantly with upregulation of cyclin D1 and downregulation of p27Kip1. On the contrary, knockdown of HOXB7 caused G(1)-S-phase arrest, downregulation of cyclin D1 and upregulation of p27Kip1. Enforced expression of HOXB7 could enhance PI3K/AKT and MAPK pathway activity. CONCLUSION: Our findings suggest that HOXB7 protein, as a valuable marker of CRC prognosis, plays an important role in the development and progression of human CRC.

Prognostic analysis and complications of traumatic carotid cavernous fistulas after treatment with detachable balloon and/or coil embolization.

OBJECTIVE: To explore the causes of the formation of traumatic carotid-cavernous fistulas and the therapeutic effect of detachable balloon and/or coil embolization and the prevention of its complications. METHODS: From October, 1992 to March, 2002, 17 patients with traumatic carotid-cavernous fistulas were treated with detachable balloon and/or coil embolization in our hospital. The clinical data and imaging features of CT, MR and selective angiogram of these patients were analyzed. RESULTS: One week after treatment with embolization, the clinical symptoms of the 17 patients were remitted, and optic cacophony, nystagmus, exophthalmos and dropsy of conjunctiva disappeared. Two patients manifested surgical complications, one patient died. Sixteen patients survived. They were all followed up for more than 2 years, which showed one patient had handicap in movement, and in one patient the signs and symptoms of traumatic carotid-cavernous fistulas reoccurred 2 months after treatment. CONCLUSIONS: The detachable balloon and/or coil embolization is safe and reliable. It is a good method to treat traumatic carotid-cavernous fistulas.