GLIPR1 regulates the TIMP1-CD63-ITGB1-AKT signaling pathway in glioma cells and induces malignant transformation of astroglioma.

Background: Astrocytoma (ACM) is characterized by high recurrence rate, high mortality, and extremely poor clinical prognosis. The new diagnostic and prognostic tumor markers related to ACM was found to improve the diagnosis rate and reduce the poor prognosis. Methods: The activity of SHC-44 and SW1783 cells under the regulation of glioma pathogenesis-related protein 1 (GLIPR1) was investigated by CCK8 analysis. The effect of GLIPR1 on the proliferation of SHC-44 and SW1783 cells was analyzed by cell colony-forming experiment. The migration of SHC-44 and SW1783 cells under the regulation of GLIPR1 was analyzed by transwell assay. The effects of GLIPR1 on the invasion and migration of SHC-44 and SW1783 cells were analyzed by cell scratch test and transwell assay. Immunofluorescence and Co-IP assays were employed to analyze the expression characteristics of GLIPR1 and CD63 proteins. The effect of GLIPR1 on the protein expression of GLIPR1, TIMP1, CD63, ITGB1, and AKT in SHC-44 and SW1783 cells was analyzed by western blot. The effect of anti-AKT on the protein expression of GLIPR1, TIMP1, CD63, ITGB1, and AKT in SHC-44 and SW1783 cells was performed by western blot. Results: The outcomes revealed that GLIPR1 could enhance the activity, proliferation, migration, and invasion of ACM cells, which might be associated with the activation of the TIMP1-CD63-ITGB1-AKT signaling pathway. Conclusions: Taken together, GLIPR1 might be a potential target for the prevention or management of ACM in the clinic.

Percutaneous Abdominal Puncture for Catheterization with Assistance of Guidewire in Lumboperitoneal Shunt.

BACKGROUND: When using a classic lumboperitoneal shunt, laparotomy is inevitable for peritoneal catheter implantation, which is time consuming and difficult for unskilled neurosurgeons. A minimally invasive technique of percutaneous abdominal puncture for catheterization with the assistance of guidewire is introduced in this paper. METHODS: Ten patients with communicating hydrocephalus received a lumboperitoneal shunt through percutaneous abdominal puncture for catheterization. The safety and effectiveness of percutaneous abdominal puncture for catheterization were followed up for more than 6 months. RESULTS: The surgery was successfully completed in 10 patients. The average operation time was nearly 30 minutes. No patients reported abdominal organ damage. None of the 10 patients had other complications such as peritonitis and obstruction of abdominal catheters caused by the percutaneous peritoneal puncture technique. One patient presented with intracranial aseptic inflammation postoperatively, which was controlled after repeated lumbar puncture. Another patient confirmed that the lumbar catheter was folded in 6 months postoperatively. CONCLUSIONS: The technique of percutaneous abdominal puncture for catheterization with the assistance of a guidewire is a simple, safe, and effective way to treat communicating hydrocephalus.

IL1RAP regulated by PRPRD promotes gliomas progression via inducing neuronal synapse development and neuron differentiation in vitro.

BACKGROUND: Glioma is a common fatal brain tumor that affects the central nervous system of the brain and spinal cord. METHODS: This is an original research. The morphology of M059 J cells and U373 cells were detected by microscope, cell neurite outgrowth was observed by immunofluorescence, and the expression of PRPRD and its downstream genes in HMC3 cells, M059 J cells and U373 cells were evaluated and compared with flow cytometry, immunofluorescence and Western blotting assay. RESULTS: Here we show that the expression of FBP17 on the surface of glioma cells M059 J and U373 cells is more than normal cells. Overexpression of protein tyrosine phosphatase receptor-δ (PTPRD) in M059 J and U373 cells resulted in a significant increase in the S phase of the cells, while the G2 phase of the cells decreased significantly after interference with PTPRD. And PTPRD protein is mainly distributed in HMC3 cells, M059 J and U373 cytoplasm. Moreover, overexpression of PTPRD resulted in a significant increase in the expression of interleukin 1 receptor accessory protein (IL1RAP), PPFIA1 and SLITRK2, and these genes were significantly suppressed after interference with PTPRD. CONCLUSION: This study shows that PRPRD can be used as a potential biomarker for glioma treatment. These results indicate that the PRPRD protein affects the development of neuronal synapses and neuronal differentiation by regulating IL1RAP, thereby promoting the progression of gliomas, indicating that PRPRD can be used as a potential biomarker for the treatment of gliomas.

Relationship of calcitonin gene-related peptide with disease progression and prognosis of patients with severe traumatic brain injury.

Calcitonin gene-related peptide (CGRP) has been implicated in multiple functions across many bioprocesses; however, whether CGRP is associated with severe traumatic brain injury (TBI) remains poorly understood. In this study, 96 adult patients with TBI (enrolled from September 2015 to December 2016) were divided into a mild/moderate TBI group (36 males and 25 females, aged 38 ± 13 years) and severe TBI group (22 males and 13 females, aged 38 ± 11 years) according to Glasgow Coma Scale scores. In addition, 25 healthy individuals were selected as controls (15 males and 10 females, aged 39 ± 13 years). Radioimmunoassay was used to detect serum levels of CGRP and endothelin-1 at admission and at 12, 24, 48, 72 hours, and 7 days after admission. CGRP levels were remarkably lower, but endothelin-1 levels were obviously higher in the severe TBI group compared with mild/moderate TBI and control groups. Levels of CGRP were remarkably lower, but endothelin-1 levels were obviously higher in deceased patients compared with patients who survived. Survival analysis and logistic regression showed that both CGRP and endothelin-1 levels were associated with patient mortality, with each serving as an independent risk factor for 6-month mortality of severe TBI patients. Moreover, TBI patients with lower serum CGRP levels had a higher risk of death. Thus, our retrospective analysis demonstrates the potential utility of CGRP as a new biomarker, monitoring method, and therapeutic target for TBI.

Gab3 overexpression in human glioma mediates Akt activation and tumor cell proliferation.

This current study tested expression and potential biological functions of Gab3 in human glioma. Gab3 mRNA and protein expression was significantly elevated in human glioma tissues and glioma cells. Its level was however low in normal brain tissues and primary human astrocytes. In both established (U251MG cell line) and primary human glioma cells, Gab3 knockdown by shRNA/siRNA significantly inhibited Akt activation and cell proliferation. Reversely, forced Gab3 overexpression in U251MG cells promoted Akt activation and cell proliferation. In vivo, the growth of U251MG tumors in nude mice was inhibited following expressing Gab3 shRNA. Akt activation in cancer tissues was also suppressed by Gab3 shRNA. Together, we conclude that Gab3 overexpression in human glioma mediates Akt activation and cancer cell proliferation.

Growth of glioblastoma is inhibited by miR-133-mediated EGFR suppression.

Glioblastoma multiforme (GBM) is a severe and highly lethal brain cancer, which malignancy largely stems from its growing in a relatively restrained area in the brain. Hence, the understanding of the molecular regulation of the growth of GBM is critical for improving its treatment. Dysregulation of microRNAs (miRNAs) has recently been shown to contribute to the development of GBM, whereas the role of miR-133 in GBM is unknown. Here, by qualitative reverse transcription polymerase chain reaction (RT-qPCR), we detected lower miR-133 levels in GBM tissues, compared to the paired normal brain tissue. We overexpressed or inhibited miR-133 in GBM cells. Cell growth and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. We found that overexpression of miR-133 decreased GBM cell growth and increased cell apoptosis, while depletion of miR-133 increased cell growth and decreased cell apoptosis. Bioinformatic analysis was performed, showing that miR-133 may target the 3'-untranslated region (3'-UTR) of the epidermal growth factor receptor (EGFR) that transduces cell growth signals. Further, the protein translation inhibition of EGFR by miR-133 was confirmed by a dual luciferase reporter assay. Together, these data suggest that reduced miR-133 levels in GBM tissues promotes cell growth and decreases cell apoptosis, possibly through targeting mRNA of EGFR to suppress its translation.

ROS-p53-cyclophilin-D signaling mediates salinomycin-induced glioma cell necrosis.

BACKGROUND: The primary glioblastoma multiforme (GBM) is the most malignant form of astrocytic tumor with an average survival of approximately 12-14 months. The search for novel and more efficient chemo-agents against this disease is urgent. Salinomycin induces broad anti-cancer effects; however, its role in GBM and the underlying mechanism are not clear. RESULTS: Here we found that salinomycin induced both apoptosis and necrosis in cultured glioma cells, and necrosis played a major role in contributing salinomycin's cytotoxicity. Salinomycin induced p53 translocation to mitochondria, where it formed a complex with cyclophilin-D (CyPD). This complexation was required for mitochondrial permeability transition pore (mPTP) opening and subsequent programmed necrosis. Blockade of Cyp-D by siRNA-mediated depletion or pharmacological inhibitors (cyclosporin A and sanglifehrin A) significantly suppressed salinomycin-induced glioma cell necrosis. Meanwhile, p53 stable knockdown alleviated salinomycin-induced necrosis in glioma cells. Reactive oxygen species (ROS) production was required for salinomycin-induced p53 mitochondrial translocation, mPTP opening and necrosis, and anti-oxidants n-acetylcysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) inhibited p53 translocation, mPTP opening and glioma cell death. CONCLUSIONS: Thus, salinomycin mainly induces programmed necrosis in cultured glioma cells.

Treatment of recurrent malignant gliomas with 13-cis-retinoic acid naphthalene triazole.

Glioblastoma multiforme and anaplastic astrocytoma are challenges to clinical biologists at present. The patients with glioblastoma have median survival of less than 12 months, despite advances in radiotherapeutical, chemotherapeutical and conventional surgical modalities. Retinoic acids are known to effect in vitro proliferation, differentiation, and apoptosis in colon, prostate, lung, and leukemia cancers. Retinoids are known to have anti-proliferation, anti-migration, and anti-invasive activity against human malignant gliomas, suggesting that retinoids are suitable anticancer agents to inhibit progression of tumors. Recurrent malignant cerebral gliomas have been treated with ATRA and 13-cis RA. However, the side effects associated with the use of high doses of retinoic acid demand for some more potent derivative free from such effects. The present clinical trials are undertaken to investigate the clinical safety and possible efficacy of administering retinoic acid naphthalene triazole (RANT) to patients with recurrent malignant gliomas. The toxicities observed in the patients during RANT treatment were mild. These preliminary results suggest that RANT is more potent compared to RA against recurrent malignant gliomas.

Treatment of pituitary adenomas with a transsphenoidal approach.

OBJECTIVE: To evaluate the overall therapeutic effectiveness of transsphenoidal microsurgery for pituitary adenomas and explore the surgical technique, application of new technology, and postoperative follow-up. METHODS: The clinical presentation, imaging features, endocrine examination, pathological types, conditions of operation, postoperative complications, and follow-up of 4050 patients with pituitary adenomas who had undergone transsphenoidal microsurgery from December 1981 to January 2004 were analyzed retrospectively. RESULTS: During the past 6 years, total tumor resection (under microscope) has been achieved in 97.3% of the patients with Hardy Grade I adenomas, 95.2% of Hardy Grade II, 90.4% of Hardy Grade III, and 47.4% of Hardy Grade IV. The percentages of total and subtotal resection achieved extended from 87.6% before 1987 to 96.9% in 2003. CONCLUSION: With the improvement of microsurgical technique and application of novel technology, the indications for transsphenoidal microsurgery for pituitary adenomas were increasingly extended. We believe that more than 90% of pituitary adenomas could be treated by the transsphenoidal approach and totally removed through the microscope. The transnasal perpendicular plate-sphenoid sinus approach will be the dominant mode. Routine postoperative radiotherapy is not required for patients with total resection.

[The clinical evaluation of patients with pituitary adenomas undergone transsphenoidal microsurgery].

OBJECTIVE: To evaluate the overall effect of transsphenoidal microsurgery for pituitary adenomas in recent 5 years and to discuss the surgical technique, application of new technology and postoperative follow-up results. METHODS: The clinical presentation, image characteristics, endocrinal findings, pathological types, tumor removal percentage, postoperative complication and follow-up of 1 462 patients with pituitary adenomas who underwent the transsphenoidal microsurgery from 1997 to 2002 were analysed retrospectively. RESULTS: Total rate of tumor removal for the patients achieved 97.0% in the patients with Hardy I adenomas, 95.2% with Hardy II, 90.5% with Hardy III, and 47.4% with Hardy IV respectively. A significant postoperative improvement both in clinical symptoms and endocrinal parameters was achieved. The tumor recurrence rate was 0.3%. CONCLUSIONS: With the improvement of microsurgical technique and application of novel technology, the indication of transsphenoidal microsurgery for pituitary adenomas was increasingly extended. Endoscope and(/or) neuronavigation-assisted microsurgery via transsphenoidal approach should be of the first choice for the treatment of pituitary adenomas. The routine postoperative radiotherapy is not required for patients with total tumor removal.