Gankyrin-mediated interaction between cancer cells and tumor-associated macrophages facilitates prostate cancer progression and androgen deprivation therapy resistance.

Increasing evidence reveals that the interaction between tumor cells and tumor-associated macrophages (TAMs) facilitates the progression of prostate cancer, but the related mechanisms remained unclear. This study determined how gankyrin, a component of the 19S regulatory complex of the 26S proteasome, regulates the progression and androgen deprivation therapy (ADT) resistance of prostate cancer through tumor cell-TAM interactions. In vitro functional experiments and in vivo subcutaneous tumor models were used to explore the biological role and molecular mechanisms of gankyrin in prostate cancer cell-TAM interactions. 234 prostate cancer patients were randomly divided into training and validation cohorts to examine the prognostic value of gankyrin through immunohistochemistry (IHC) and statistical analyses, and high gankyrin expression was correlated with poor prognosis. In addition, gankyrin facilitated the progression and ADT resistance of prostate cancer. Mechanistically, gankyrin recruited and upregulated non-POU-domain-containing octamer-binding protein (NONO) expression, resulting in increased androgen receptor (AR) expression. AR then bound to the high-mobility group box 1 (HMGB1) promoter to trigger HMGB1 transcription, expression, and secretion. Moreover, HMGB1 was found to promote the recruitment and activation of TAMs, which secrete IL-6 to reciprocally promote prostate cancer progression, ADT resistance and gankyrin expression via STAT3, resulting in formation of a gankyrin/NONO/AR/HMGB1/IL-6/STAT3 positive feedback loop. Furthermore, targeting the interaction between tumor cells and TAMs by blocking this loop inhibited ADT resistance in a tumor xenograft model. Taken together, the data show that gankyrin serves as a reliable prognostic indicator and therapeutic target for prostate cancer patients.

An easy long-acting BMP7 release system based on biopolymer nanoparticles for inducing osteogenic differentiation of adipose mesenchymal stem cells.

In contrast to the early acting bone morphogenetic protein 2, bone morphogenetic protein 7 (BMP7) plays a decisive role mainly in the late stages of bone formation. To overcome deactivation and degradation of expensive BMP7, we designed a novel long-acting BMP7 release system based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) nanoparticles to enable the induction of osteogenic differentiation in human adipose mesenchymal stem cells (ADSCs). In order to improve the encapsulation efficiency of BMP7 and avoid damage by organic solvents, BMP7 was modified and protected using the biosurfactant soybean lecithin. In an in vitro test, BMP7-soybean lecithin-P34HB nanoparticles (BMP7-SPNPs) showed a short initial burst of BMP7 release during the first 24h, followed by a steady increase to a cumulative 80% release in 20days. Compared with the rapid release of control P34HB nanoparticles without soybean phospholipids loaded with BMP7 without soybean lecithin, BMP7-SPNPs significantly reduced the initial burst of BMP7 release and stabilized the content of BMP7 to allow long-term osteogenic differentiation during the late phase of bone development. Human ADSCs treated with BMP7-SPNPs showed higher alkaline phosphatase activity and higher expression levels of genetic markers of osteogenic differentiation compared with the control group. Thus, the results indicate that BMP7-SPNPs can be used as a rapid and long-acting BMP7 delivery system for osteogenic differentiation.

SMAD3 silencing enhances DNA damage in radiation therapy by interacting with MRE11-RAD50-NBS1 complex in glioma.

Radiotherapy is the major treatment modality for malignant glioma. However, the treatment response of radiotherapy is suboptimal due to resistance. Here we aimed to explore the effect and mechanism of Mothers against decapentaplegic homologue (SMAD3) silencing in sensitizing malignant glioma to radiotherapy. Clonogenic assay was used to evaluate the sensitivity of glioma cells to increasing doses of radiation. Glioma cells were transfected with small-interfering RNAs (siRNAs) specific to SMAD3. Overexpression of SMAD3 was achieved by transfecting expression plasmid encoding SMAD3 cDNA. Changes in MRE11-RAD50-NBS1 mRNA and protein levels were assessed through qPCR analysis and western blot analysis, respectively. Chromatin immunoprecipitation (ChIP) was used to confirm the interaction between SMAD3 and MRE11-RAD50-NBS1 (MRN) complex. Silencing of SMAD3 increased sensitivity of glioma cells to radiotherapy. MRE11, RAD50 and NBS1 were overexpressed in response to radiotherapy, which was attenuated by SMAD3 silencing while boosted by SMAD3 overexpression. ChIP analysis confirmed the interaction of SMAD3 with MRE11, RAD50 and NBS1 under radiotherapy, which was inhibited by SMAD3 silencing. SMAD3 silencing is an effective strategy for sensitizing glioma to radiotherapy, which is mediated by the interaction of SMAD3 with the MRN complex.

SNHG29 regulates miR-223-3p/CTNND1 axis to promote glioblastoma progression via Wnt/ß-catenin signaling pathway.

BACKGROUND: Glioblastoma has been seen as the most common malignancy of brain tumor. Emerging reports has claimed that SNHG29 (LRRC75A-AS1) was involved in several biological processes via modulation of signaling pathway, and served as an malignant facilitatorin osteosarcoma. However, the specific role of SNHG29 in glioblastoma remains unknown. METHODS: RT-qPCR and microarray were operated to measure genes expression. Western blot was performed to examine protein expression. CCK-8 and colony formation assays were used to evaluate cell proliferation. Cell migration was tested by transwell assay. Nuclear-cytoplasmic fractionation was conducted to locate SNHG29. The binding capacity of miR-223-3p to SNHG29 or CTNND1 3'UTR was verified by RIP and luciferase reporter assay. RESULTS: SNHG29 presented high expression in glioblastoma to boost cell proliferation, migration and EMT process. In addition, miR-223-3p was validated to bind with SNHG29 after prediction and screening. Furthermore, miR-223-3p was proved to be a negative regulator for its target CTNND1. Then, the inhibition on cell proliferation, migration and EMT process resulted from SNHG29 knockdown was recovered by CTNND1 overexpression. At last, the inhibitive impacts on cell proliferation, migration and EMT process of CTNND1 deficiency was abrogated by LiCl. CONCLUSIONS: In conclusion, SNHG29 regulates miR-223-3p/CTNND1 axis to promote glioblastoma progression via Wnt/ß-catenin signaling pathway, offering a potential therapeutic point for glioblastoma patients.

High-Precision Lens-Less Flow Cytometer on a Chip.

We present a flow cytometer on a microfluidic chip that integrates an inline lens-free holographic microscope. High-speed cell analysis necessitates that cells flow through the microfluidic channel at a high velocity, but the image sensor of the in-line holographic microscope needs a long exposure time. Therefore, to solve this problem, this paper proposes an S-type micro-channel and a pulse injection method. To increase the speed and accuracy of the hologram reconstruction, we improve the iterative initial constraint method and propose a background removal method. The focus images and cell concentrations can be accurately calculated by the developed method. Using whole blood cells to test the cell counting precision, we find that the cell counting error of the proposed method is less than 2%. This result shows that the on-chip flow cytometer has high precision. Due to its low price and small size, this flow cytometer is suitable for environments far away from laboratories, such as underdeveloped areas and outdoors, and it is especially suitable for point-of-care testing (POCT).

Enhanced radiosensitization of human glioblastoma multiforme cells with phosphorylated peptides derived from Gli2.

Glioma-Associated Oncogene Family Zinc Finger 2 (Gli2) seems to be the major nuclear effector of Sonic Hedgehog (SHH) signaling to regulate self-renewal and tumorigenic potential of Glioblastoma multiforme (GBM) cells. Three phosphorylated peptides derived from Gli2 were synthesized and combined with cell-penetrating peptide Tat-(47-57) (AYGRKKRRQRRR). Western Blot was applied to detect the phosphorylation level of Gli2 and cell division protein kinase 6 (CDK6) luciferase reporter was utilized to detect the transcriptional activator function of Gli2. Clonogenic survival assay and apoptosis assay were used to testify the radiosensitization effect. The mixed three phosphorylated peptides derived from Gli2 increased the phosphorylation level of Gli2 and decreased Gli2 transcriptional activator activity significantly than the individually used peptide. The mixed three phosphorylated peptides showed greater radiation-sensitizing effects in GBM cells in clonogenic and survival assay compared with control peptide. We present here a novel rational strategy for developing phosphorylated peptides derived from Gli2 to decrease Gli2 transcriptional activator activity and such administration could radiosensitize GBM.

Effect of low-energy extracorporeal shock wave on vascular regeneration after spinal cord injury and the recovery of motor function.

BACKGROUND: Latest studies show that low-energy extracorporeal shock wave therapy (ESWT) can upregulate levels of vascular endothelial growth factor (VEGF). VEGF can ease nervous tissue harm after spinal cord injury (SCI). This study aims to explore whether low-energy ESWT can promote expression of VEGF, protect nervous tissue after SCI, and improve motor function. METHODS: Ninety adult female rats were divided into the following groups: Group A (simple laminectomy), Group B (laminectomy and low-energy ESWT), Group C (spinal cord injury), and Group D (spinal cord injury and low-energy ESWT). Impinger was used to cause thoracic spinal cord injury. Low-energy ESWT was applied as treatment after injury three times a week, for 3 weeks. After SCI, the Basso, Beattie, and Bresnahan (BBB) scale was used to evaluate motor function over a period of 42 days at different time points. Hematoxylin and eosin (HE) staining was used to evaluate nerve tissue injury. Neuronal nuclear antigen (NeuN) staining was also used to evaluate loss of neurons. Polymerase chain reaction was used to detect messenger RNA (mRNA) expression of VEGF and its receptor fms-like tyrosine kinase 1 (Flt-1). Immunostaining was used to evaluate VEGF protein expression level in myeloid tissue. RESULTS: BBB scores of Groups A and B showed no significant result related to dyskinesia. HE and NeuN staining indicated that only using low-energy ESWT could not cause damage of nervous tissue in Group B. Recovery of motor function at 7, 35, and 42 days after SCI in Group D was better than that in Group C (P<0.05). Compared with Group C, number of NeuN-positive cells at 42 days after SCI increased significantly (P<0.05). The mRNA levels of VEGF and Flt-1 and VEGF expression at 7 days after SCI in Group D were significantly higher than those in Group C (P<0.05). CONCLUSION: Low-energy ESWT promotes expression of VEGF, decreases secondary damage of nerve tissue, and improves recovery of motor function. It can be regarded as one mode of clinical routine adjunctive therapy for spinal injury.

Association between XRCC1 Arg399Gln polymorphism and glioma risk in a Chinese population: a case-control study.

AIM: In China, the incidence rates of glioma tend to be increased, however, the genetic contribution to its etiology is not well-understood. The aim of this study is to evaluate the association of XRCC1 Arg399Gln polymorphism with glioma risk in a Chinese population. MATERIALS AND METHODS: We conducted a case-control study on 387 patients with glioma and 400 cancer-free controls between 2004 and 2014. Peripheral blood samples of both groups were processed for DNA extraction and genotyping of the XRCC1 Arg399Gln polymorphism using PCR-RFLP. Comparison of the distribution of Arg399Gln genotypes in the study groups was performed by means of 2-sided contingency tables using the χ(2) test. Hazard ratios (HRs) were estimated by Cox proportional hazard regression model. RESULTS: When the AA genotype was used as the reference group, the GG genotype was associated with significantly increased risk for glioma (adjusted OR = 3.18, 95% CI = 1.38-3.88; P = 0.017). Under the dominant model of inheritance, the AG + GG genotype was associated with significantly increased risk for glioma (adjusted OR =2.33, 95% CI = 1.12-5.81; P = 0.023). When the A allele was used as the reference group, the G allele was associated with increased glioma risk (adjusted OR, 2.44, 95% CI, 1.76-4.18; P = 0.003). CONCLUSION: Our data suggests that XRCC1 Arg399Gln polymorphism contribute to increased risk of glioma, which may be susceptibility biomarkers for glioma.

Clinical characteristics and neurologic recovery of patients with cervical spinal tuberculosis: should conservative treatment be preferred? A retrospective follow-up study of 115 cases.

OBJECTIVE: To present the clinical characteristics and prognostic factors of neurologic recovery in patients with cervical spinal tuberculosis (CST). METHODS: General description and multivariate analysis were used to detect possible predictors of the outcome of patients with neurologic deficit. Follow-up data were used to generate a Kaplan-Meier curve of neurologic recovery. RESULTS: Protective factors in neurologic recovery included less involved vertebrae, surgery, and higher Japanese Orthopaedic Association score before treatment; not shorter symptom duration was not a protective factor. Normal neurologic function was present in 30% of patients 6 months after treatment, in 56% of patients 12 months after treatment, and in 93% of patients 28 months after treatment. The cumulative complete neurologic recovery rates at 6 months, 12 months, and 28 months were 44%, 68%, and 91.7% in the surgery group and 16.7%, 38.8%, and 94.4% in the nonsurgery group. CONCLUSIONS: Surgery and Japanese Orthopaedic Association score before treatment are important predictors of neurologic recovery in patients with CST. A neurologic recovery curve could predict neurologic recovery in patients with CST and indicate in patients with neurologic deficit how long it will take to achieve complete neurologic recovery. The effect of surgery is quick, and the effect of conservative treatment is slower, but no difference in neurologic recovery was found in the long-term. Conservative treatment should be tried in every patient with CST with no obvious indication for surgery. In contrast to patients with tuberculosis without cervical spine involvement but with more complications, comprehensive conservative therapy should be preferred for patients with neurologic deficit to avoid unnecessary surgery and overtreatment and to conserve medical resources. Indications for surgical intervention for CST should be carefully selected.

Vertebral osteomyelitis and epidural abscess due to Aspergillus nidulans resulting in spinal cord compression: case report and literature review.

Vertebral osteomyelitis caused by Aspergillus nidulans is rare and usually affects immunocompromised patients. This report presents a case of thoracic vertebral osteomyelitis with epidural abscesses due to A. nidulans in a 40-year-old immunocompetent female who presented with back pain, numbness and weakness of both lower limbs. Magnetic resonance imaging demonstrated osteomyelitis involving the thoracic (T)1-T3 vertebral bodies with epidural abscesses, resulting in spinal compression. The patient underwent a decompression laminectomy of T1-T3 and debridement of the thoracic epidural inflammatory granuloma. Histopathology revealed fungal granulomatous inflammation. The patient received 6 mg/kg voriconazole every 12 h (loading dose on day 1) followed by 4 mg/kg voriconazole twice daily for 1 month, administered intravenously. The patient returned with recurrent back pain 16 months after initial presentation. A. nidulans was identified by fungal culture and polymerase chain reaction. The patient showed no evidence of recurrence 1 year after a 6-month course of oral voriconazole. The key to the effective treatment of Aspergillus osteomyelitis is not to excise the abscess, but to administer systemic antifungal drug therapy.

[Neuroendoscope-assisted surgical treatment of spinal dural arteriovenous fistulas].

OBJECTIVE: To study the utility of neuroendoscope-assisted surgery in the treatment of spinal dural arteriovenous fistulas. METHODS: From November 2008 to November 2010, 8 cases of spinal dural arteriovenous fistulas underwent neuroendoscope-assisted surgical treatment by a hemilaminectomy approach. Retrospective analyses were performed for their clinical manifestations, imaging findings, surgical approaches, postoperative recovery and follow-up profiles. RESULTS: All were of single fistula. Under the assistance of neuroendoscope, the fistulas were found intra-operatively and the draining veins disconnected successfully. The results of post-operative angiography showed the disappearance of all draining veins. After a follow-up period of 3 - 35 months, 2 cases became asymptomatic, 5 cases improved obviously and 1 case had no change. CONCLUSION: Neuroendoscope-assisted surgery is mini-invasive, safe and effective in the treatment of spinal dural arteriovenous fistulas.

Multilevel myelopathy associated with pseudohypoparathyroidism simulating diffuse skeletal hyperostosis: a case report and literature review.

STUDY DESIGN: A case report and review of previous literature are presented. OBJECTIVE: The objective of this manuscript was to report a case of pseudohypoparathyroidism (PHP) 1a simulating diffuse idiopathic skeletal hyperostosis and resulting in spinal cord compression, and discuss the pathogenesis of this disease. SUMMARY OF BACKGROUND DATA: Spinal cord compression due to PHP is not common, to the authors' knowledge, none of the previous reported cases simulated diffuse idiopathic skeletal hyperostosis. METHODS: The patient's history, clinical examination, imaging findings, and treatment were reported; and the pathogenesis was discussed. RESULTS: Characteristic findings were revealed from imaging studies, a multiplane reconstruction of the computed tomography images, and magnetic resonance imaging. The patient was treated by 2-stage posterior decompression on the basis of the images. A mild improvement was observed after the surgeries and the patient's neurology was not completely restored after 6 months. CONCLUSION: We reported a rare case of skeletal and ligamentous abnormality resulting in spinal cord compression associated with PHP. A multiplane reconstruction of the computed tomography images was very necessary for diagnosis and treatment of this case. The unfavorable neurologic restoration might be due to the severe injury of the spinal cord caused by diffuse ossification of the posterior longitudinal ligament and ligamentum flavum.

[The methylation analysis of EMP3 and PCDH-gamma-A11 gene in human glioma].

OBJECTIVES: To study the relationship between promoter methylation and mRNA expressions of EMP3 and PCDH-gamma-A11 genes in human glioma, and to analyze the regulation mechanism of promoter methylation in the progression of glioma. METHODS: The promoter methylation of EMP3 and PCDH-gamma-A11 was studied by a methylation specific PCR in 88 primary astrocytoma, 10 normal brain tissues and 2 glioma cell lines. The mRNA expressions were detected by real-time PCR in 30 primary glioma and 10 normal brain tissues. The correlations of their promoter methylation, mRNA expressions and clinicopathologic characteristics were analyzed. The promoter methylation were also detected in U251 and SHG-44 cell lines. RESULTS: The promoter methylation of EMP3 was detected in 42 tumors (47.7%) and the methylation of PCDH-gamma-A11 was detected in 76 tumors (86.4%). Their mRNA expressions were all significantly decreased in different pathological grade astrocytomas compared to the normal brain tissues (P < 0.01). Their expressions were suppressed but could be reactivated by 5-aza-deoxycytidine in U251 and SHG-44 cell lines. CONCLUSIONS: The promoter methylation of EMP3 and PCDH-gamma-A11 genes may lead to the down-regulation of their mRNA levels in glioma. The promoter methylation and mRNA expressions of EMP3 and PCDH-gamma-A11 are closely related with the malignant development of glioma. The promoter methylation of the two genes may provide clues to evaluation of glioma malignancy as well as its prognosis. It also gives us an insight for future glioma medical therapy with a demethylating agent.

A cervical myelopathy caused by invaginated anomaly of laminae of the axis in spina bifida occulta with hypoplasia of the atlas: case report.

STUDY DESIGN: A case report and review of previous literature are presented. OBJECTIVE: The objective of this manuscript was to report a case of cervical myelopathy caused by invaginated anomalous laminae of the axis in a spina bifida occulta patient with hypoplasia of the arch of the atlas and to discuss the etiology of this disease. SUMMARY OF BACKGROUND DATA: To the authors' knowledge, few cases of cervical myelopathy due to invaginated anomalous laminae of the axis have been reported, none of which is combined with hypoplasia of the arch of atlas. Treatment was surgical removal of the invaginated laminae. METHODS: The patient's history, clinical examination, imaging findings, and treatment were reported, and the etiology was discussed. RESULTS: Characteristic findings were revealed from imaging studies and multiplane reconstruction of the computed tomography images. The patient was treated with a posterior decompressive operation based on the images. A rapid improvement was observed after the surgery, and the patient's neurology was completely restored 1 month later. CONCLUSION: We reported a rare characteristic anomaly of the laminae of the axis with hypoplasia of the posterior arch of atlas. A multiplane reconstruction of the computed tomography images was very necessary for treatment of this case. Possible causes of this anomaly may be the failure of ossification or fusion of the embryological term, whereas invagination of the osteophyte may be associated with the traction of the dense fibrous band during growth and development. Surgical removal of the laminae could result in a satisfactory outcome.

[The methylation and mRNA expression of SLC5A8 and TMS1/ASC genes in human glioma].

OBJECTIVE: To study the methylation status of the SLC5A8 and TMS1/ASC genes, candidate tumor-inhibiting genes closely related to the central nervous system, in the promoter regions, the mRNA expression of these 2 genes, and their correlation with the clinical characteristics in human glioma. METHODS: The methylation status of SLC5A8 and TMS1/ASC genes in the promoter regions was studied by methylation specific PCR (MSP) in the specimens of primary astrocytoma from 88 patients, 55 males and 33 females, aged 12 - 81, and 10 specimens of normal brain tissue, all obtained during operation, and in the human glioma cells of the lines U251 and SHG-44. The mRNA expression levels of SLC5A8 and TMS1/ASC genes in 30 specimens of primary glioma and 10 specimens of normal brain tissue were determined by conventional RT-PCR and real-time PCR. 5-Aza-2'-deoxycytidine (5-Aza-CdR), a demethylating agent, was added into the culture fluid of the U251 and SHG-44 cells, and then real-time PCR was used to the methylation status and mRNA expression levels of the SLC5A8 and TMS1/ASC genes. RESULTS: MSP showed that the SLC5A8 promoter region was hypermethylated in 62 of the 88 specimens of astrocytoma (70.45%) and the TMS1/ASC promoter region was hypermethylated in 51 of the88 specimens of astrocytoma (57.95%). But no methylation of SLC5A8 and TMS1/ASC promoter was detected in the 10 specimens of normal brain tissue. The mRNA expression of SLC5A8 gene and the mRNA expression of TMS1/ASC gene in the specimens of astrocytoma of different pathological grades were all significantly decreased compared to the specimens of normal brain tissue (all P < 0.05). The mRNA expression of SLC5A8 gene was not significantly related to the age and sex, however, the mRNA expression of TMS1/ASC was significantly higher in the age group > 60 than in other age groups (all P < 0.05). Both U251 and SHG-44 glioma cells showed methylation of SLC5A8 and TMS1/ASC genes and after the treatment of 5-Aza-CdR both genes showed reactivated mRNA expression. CONCLUSION: Hypermethylation of SLC5A8 and TMS1/ASC genes in the promoter regions may play an important role in the down-regulation of their mRNA levels in glioma. The methylation frequency and mRNA levels of SLC5A8 or TMS1/ASC genes are closely related to the malignant development of glioma.

Number concentration and size distributions of submicron particles in jinan urban area: characteristics in summer and winter.

The aerosol number concentration and size distribution were measured with the newly developed Wide-range Particle Spectrometer in summer and winter of 2006 at the urban site of Jinan City. Here reported the characteristics of fine particles of the different observation seasons. Relative high number concentrations for the particles in the diameter range of 10-500 nm were observed in both seasons. It was found that the dominant number distributed in particle diameter smaller than 100 nm and the percentage over the number concentration of all air particles is much higher than what has been measured in other urban sites over the world. The number mean diameter in summer was much smaller than in winter, strongly suggesting the different origin of ultrafine particles in different seasons. That is, particles in ultrafine mode mainly came from nucleation and new particle formation in summer while from traffic emission in winter. The diurnal variation also supported this point. Number concentration in the diameter range of 10-200 nm got their peak values at noontime, well correlated with the mixing ratio of SO2 and the intensity of solar radiation in summer. While in winter, those in the same diameter range showed the main peaks during the traffic hours happened in the morning and evening.

Expression analyses of 27 DNA repair genes in astrocytoma by TaqMan low-density array.

DNA repair systems act to maintain genome integrity in the face of replication errors, environmental insults, and the cumulative effects of age. The mRNA expressions of 27 genes of the DNA repair system as well as their correlation with the clinical characteristics were studied in human astrocytoma. We applied TaqMan low-density array to investigate the mRNA expressions of 27 DNA repair genes in 40 astrocytoma tissues (10 of grade II, 10 of grade III, and 20 of grade IV, according to the WHO Grading System). And the normal brain tissues from 10 non-astrocytoma patients were collected as the control. In addition, correlation of their mRNA levels with clinical characteristics was also analyzed. We found that the expression of the 13 genes were significantly (P<0.01) down-regulated in grade II, III, IV of astrocytoma compared to normal brain tissues, including ERCC1, ERCC2, ERCC3, ERCC4, MGMT, MLH1, MLH3, NTHL1, OGG1, RAD50, SMUG1, XRCC4 and XRCC5. Meanwhile, we found that the expression of MSH2, MSH6, NUDT1 and XRCC3 were only significantly lower in grade II and III of astrocytoma, and the expression of MRE11A and MUS81 were only significantly lower in grade III and IV. But the expression of MPG, MSH3, MUTHY and RAD51 were not changed in any grade of astrocytoma. Furthermore, we found that the decrease expression of eight genes was significantly (P<0.05) associated with a poor prognosis, including ERCC3, ERCC4, MLH3, MRE11A, NTHL1, RAD50, XRCC4 and XRCC5. We suggest that TaqMan low-density array is an effective multivariate technique to examine the expression of DNA repair genes in astrocytomas, which can be applied to identify tumor-specific genes. We also suggest that the down-regulation of some DNA repair genes may be associated with pathogenesis and poor prognosis of astrocytoma.

Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma.

LATS1 and LATS2 are tumor suppressor genes implicated in the regulation of cell cycle, but their methylation statuses are still unknown in human astrocytoma. Here, we found that the promoter hypermethylation frequencies of LATS1 and LATS1 were 63.66% (56/88) and 71.5% (63/88) in 88 astrocytomas by methylation-specific PCR. But no methylation of LATS1 and LATS2 promoter was detected in the 10 normal brain tissues. There was an increased methylation frequency of LATS1 and LATS2 with the malignant development of astrcytoma. By real-time PCR, the mRNA expression of LATS1 or LATS2 was detected significantly decreased in different pathological grade astrocytomas (P<0.05). And the mRNA levels of LATS1 and LATS2 in astrocytomas with hypermethylation were both significantly (P<0.01) lower than those without methylation. The methylation of LATS1 and LATS2 was detected in U251 and SHG-44 cell lines, and 5-aza-deoxycytidine could restore their expression to induce cell apoptosis. Our results suggested that LATS1 and LATS2 mRNA was down-regulated in astrocytoma by hypermethylation of the promoter. The methylation and mRNA expression of LATS1 and LATS2 may provide useful clues to the development of the diagnostic assays for astrocytoma. Our results also suggested that LATS1 and LATS2 may be a useful target for astrocytoma therapy.

Traumatic subdural hydroma developing into chronic subdural hematoma.

OBJECTIVE: To probe the incidence, pathogenesis and clinical characteristics of traumatic subdural hydroma (TSH) developing into chronic subdural hematoma (CSDH). METHODS: We retrospectively analyzed the clinical data of 32 patients with TSH developing into CSDH and reviewed related literature. RESULTS: 16.7% of TSH developed into CSDH in this study. The time of evolution was from 22 to 100 days after head injury. All the patients were cured with hematoma drainage. CONCLUSIONS: TSH is one of the origins of CSDH. The clinical characteristics of TSH developing into CSDH follow that the ages of the patients are polarized, that the evolution often happens in the patients with small chronic hydromas and being treated conservatively, that the patients are usually injured deceleratedly and that the accompanying cerebral damage is often very mild.