Tianhong Pan

MiR-125b is critical for the suppression of human U251 glioma stem cell proliferation

Stem cells are unique in their ability to self-renew and maintain tissue homoeostasis by differentiating into different cell types to replace aged or damaged cells. The key characteristic of the stem cell is its capacity to divide for long periods of time. MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs. miR-125b, one of neuronal miRNAs, recently was found to be necessary for stem cell fission to bypass the normal G1/S checkpoint and make stem cells insensitive to chemotherapy signals, which normally stop the cell cycle at the G1/S transition. Given the insensitivity of gliomas to chemotherapy and the hypothesis that glioma stem cells cause resistance to drug therapy, exploring the functions and mechanisms of miR-125b in glioma stem cells would be valuable. In this study, we found that miR-125b was downregulated in human U251 glioma stem cells, therefore suggesting that its upregulation can lead to the growth inhibition of U251 glioma stem cells in vitro. Further research on the mechanism demonstrated that inhibition of miR-125b-induced U251 glioma stem cell proliferation was due to cell cycle arrest at the G1/S transition and involved the cell cycle regulated proteins CDK6 and CDC25A; miR-125b overexpression decreased CDK6 and CDC25A expression. These findings underscore the potential of miR-125b to regulate the proliferation of U251 glioma stem cells through the cell cycle regulated proteins CDK6 and CDC25A.

MicroRNA-21 inhibitor sensitizes human glioblastoma U251 stem cells to chemotherapeutic drug temozolomide.

MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs. In mammals, their function mainly represses the target mRNA transcripts via imperfect complementary sequences in the 3′UTR of target mRNAs. Several miRNAs have been recently reported to be involved in modulation of glioma development, especially some upregulated miRNAs, such as microRNA-21 (miR-21), which has been found to function as an oncogene in cultured glioblastoma multiforme cells. Temozolomide (TMZ), an alkylating agent, is a promising chemotherapeutic agent for treating glioblastoma. Although chemotherapy with temozolomide may contain tumor growth for some months, invariable tumor recurrence suggests that cancer stem cells maintaining these tumors persist. Previous research showed that TMZ could inhibit the proliferation of human glioblastoma stem cells (GSC), but not induced apoptosis, which could supply the chance for glioblastoma recurrence. Accumulating evidence indicated that downregulation of miR-21 in glioblastoma cells caused repression of growth and increased apoptosis, all of which could theoretically enhance the chemotherapeutic effects of cancer therapy. In this study, we aimed to explore whether miR-21 downregulation could enhance the chemotherapeutic effects of TMZ and induce apoptosis on GSC. Interestingly, the results demonstrated that either miR-21 inhibitor or TMZ could not induce apoptosis on GSC. However, miR-21 inhibitor combined with TMZ significantly enhanced GSC apoptosis. Taken together, a combination of miR-21 inhibitor and TMZ could be an effective therapeutic strategy for GSC apoptosis to prevent potential glioblastoma recurrence.

miR-335 promotes cell proliferation by directly targeting Rb1 in meningiomas

Meningiomas, one of the most common benign brain tumors in humans, arise from arachnoid cells in the brain meninges. Our investigations have revealed that miR-335 is a typical microRNA overexpressed in meningiomas in humans. Characterization of the effects of miR-335 overexpression in meningiomas demonstrated that elevated levels of miR-335 increased cell growth and inhibited cell cycle arrest in the G0/G1 phase in vitro; in addition, reduction of the miR-335 levels had the opposite effect on tumor growth and progression. Further, previous studies have shown that the mechanism of effect of miR-335 on the proliferation of meningioma cells is associated with alterations in the expression of human retinoblastoma 1 (Rb1). Our results indicate that miR-335 plays an essential role in the proliferation of meningioma cells by directly targeting the Rb1 signaling pathway. Thus, our results highlight a novel molecular interaction between miR-335 and Rb1, and miR-335 may represent a potential novel therapeutic agent to target the proliferation of meningioma cells.

Functional Differences of miR-125b on the Invasion of Primary Glioblastoma CD133-Negative Cells and CD133-Positive Cells

MicroRNAs (miRNAs) are small noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell development, differentiation, and homeostasis. The total number and composition of miRNAs expressed per cell at different stages of development varies widely, and the same miRNA may function differently at different stages of development. In this prospective study, we evaluated the function of miR-125b at different developmental stages of glioblastoma cells, such as primary glioblastoma cells and the corresponding stem cells. CD133 is an important surface marker in glioblastoma stem cells. We found that the upregulation of miR-125b had no effects on the invasion of primary glioblastoma CD133-negative cells but that it could inhibit the invasion of corresponding CD133-positive cells; however, the downregulation of miR-125b also had no effects on the invasion of primary glioblastoma CD133-negative cells but promoted the invasion of CD133-positive cells. Further research into the underlying mechanism demonstrated that the effects of miR-125b on the invasion of glioblastoma CD133-positive cells were associated with the alteration of the expression of MMPs (MMP-2 and MMP-9) and corresponding inhibitors (RECK and TIMP3). Our results demonstrate that miR-125b expression plays an essential role in the invasion of glioblastoma CD133-positive cells but not CD133-negative cells. Therefore, miR-125b may represent a novel target for therapy targeting the invasion of glioblastoma stem cells in the future.

Association between polymorphisms in interleukin-4Rα and interleukin-13 and glioma risk: A meta-analysis

INTRODUCTION It has been suggested that allergies are inversely associated with glioma risk. Single nucleotide polymorphisms in two allergy-related genes [interleukin (IL)-4Rα, IL-13] have been implicated in susceptibility to glioma; however, results from the published studies remained inconclusive. METHODS To derive a more precise relationship, we conducted a meta-analysis including seven case-control studies that investigated the influence of IL-4Rα rs1801275 and IL13 rs20541 polymorphisms on glioma risk. Data were extracted from these studies and pooled odds ratios (OR) with 95% confidence intervals (CI) were used to investigate the strength of the association. RESULTS Overall, the pooled analysis showed that there was no significant association between the IL-4Rα rs1801275 polymorphism and glioma risk (OR = 0.99, 95%CI: 0.79-1.25, AG/GG vs. AA). However, we found that the IL13 rs20541 variant genotypes (GA/AA) were significantly associated with reduced risk for glioma (OR = 0.85, 95%CI: 0.75-0.97, GA/AA vs. GG). In the stratified analyses by ethnicity, marginally significant association between the IL13 rs20541 polymorphism and decreased glioma risk was found among Asian populations in dominant models (OR = 0.84, 95%CI: 0.70-1.00, GA/AA vs. GG). CONCLUSIONS This meta-analysis suggests that the IL13 rs20541 but not the IL-4Rα rs1801275 polymorphism may be a genetic predictor for glioma. More studies with larger sample size are warranted to further elucidate the impact of the IL13 rs20541 polymorphism on glioma risk.

Technique of ICP Monitored Stepwise Intracranial Decompression Effectively Reduces Postoperative Complications of Severe Bifrontal Contusion.

Background Bifrontal contusion is a common clinical brain injury. In the early stage, it is often mild, but it progresses rapidly and frequently worsens suddenly. This condition can become life threatening and therefore requires surgery. Conventional decompression craniectomy is the commonly used treatment method. In this study, the effect of intracranial pressure (ICP) monitored stepwise intracranial decompression surgery on the prognosis of patients with acute severe bifrontal contusion was investigated. Method A total of 136 patients with severe bifrontal contusion combined with deteriorated intracranial hypertension admitted from March 2001 to March 2014 in our hospital were selected and randomly divided into two groups, i.e., a conventional decompression group and an ICP monitored stepwise intracranial decompression group (68 patients each), to conduct a retrospective study. The incidence rates of acute intraoperative encephalocele, delayed hematomas, and postoperative cerebral infarctions and the Glasgow outcome scores (GOSs) 6 months after the surgery were compared between the two groups. Results (1) The incidence rates of acute encephalocele and contralateral delayed epidural hematoma in the stepwise decompression surgery group were significantly lower than those in the conventional decompression group; the differences were statistically significant (P < 0.05); (2) 6 months after the surgery, the incidence of vegetative state and mortality in the stepwise decompression group were significantly lower than those in the conventional decompression group (P < 0.05); the rate of favorable prognosis in the stepwise decompression group was also significantly higher than that in the conventional decompression group (P < 0.05). Conclusion The ICP monitored stepwise intracranial decompression technique reduced the perioperative complications of traumatic brain injury through the gradual release of ICP and was beneficial to the prognosis of severe traumatic brain injury treatment.

Effective treatment via early cranioplasty for intractable contralateral subdural effusion after standard decompressive craniectomy in patients with severe traumatic brain injury

OBJECTIVE This study aimed to introduce an effective treatment for intractable contralateral subdural effusion after standard decompressive craniectomy in patients with severe traumatic brain injury (TBI) and to analyze the underlying mechanism. METHODS A retrospective analysis was performed in 13 patients with severe traumatic craniocerebral injury showing complicated intractable contralateral subdural effusion after standard decompressive craniectomy, in whom satisfactory results were not obtained from treatments, including compression bandaging, head-down bed rest (HDBR), continuing lumbar drainage, and Ommaya catheter drainage. Among these patients, 6 underwent temporal muscle sticking, while 7 underwent early cranioplasty. The postoperative changes in the subdural effusion were observed. RESULTS In the 6 patients who underwent temporal muscle sticking and the 7 who underwent early cranioplasty, the subdural effusion completely resolved or was significantly reduced within one month, and no recurrence was observed in the 6-month follow-up period. However, secondary bilateral cranioplasty was still necessary in the postoperative 3-6 months for the patients who underwent temporal muscle sticking. In the early cranioplasty group, there were three total operations, and the average length of stay (ALOS) was 76days. In the temporal muscle sticking group, there were four total operations, and the ALOS was 56.1days. A retrospective analysis of surgical pain showed that 100% of the patients in the first group experienced unacceptable suffering, while 14.3% of the patients in the second group experienced pain. CONCLUSION Early cranioplasty is an effective, economical, and less painful treatment for intractable contralateral subdural effusion after standard decompressive craniectomy.

A Case Report of Severe Traumatic Brain Injury and Intractable Subdural Effusion

Traumatic subdural effusion is an accumulation of the cerebrospinal fluid in the subdural space after traumatic brain injury. However, the pathogenesis and clinical significance are uncertain. As the majority of patients with subdural effusion do not show a mass effect, most subdural effusions resolve when the brain is well expanded. Thus, surgery is rarely required. We have not seen any reports of a deteriorating subdural effusion using a combined treatment of Ommaya reservoirs and encephalo-myosynangiosis. In this report, we showed that the patient, who had developed an apparent mass effect and had deteriorating clinical manifestations, needed such a combined surgery.

A Case Report of Skull Hemangioma

Intraosseous hemangiomas are benign vascular tumors that are encountered most commonly in the vertebrae and rarely in the skull. Primary intraosseus hemangiomas of the skull are extremely rare. Here, we report a patient with an incidental finding on magnetic resonance imaging of an intraosseous hemangioma lesion in the right parietal bone. We present this case because it is primary and rare, but more importantly, at surgery, it was found that these lesions infiltrated the local dura mater and subcutaneous tissue that was inconsistent with the benign