Short- and long-term efficacy of sustained-release chemotherapy in tumor bed interstitium combined with surgical resection for recurrent malignant glioma.

OBJECTIVE: To discuss and analyze the short- and long-term curative effect of sustained-release chemotherapy combined with surgical resection on recurrent malignant glioma. METHODS: The clinical data of 137 patients with recurrent glioma admitted to our hospital from March 2016 to July 2018 were retrospectively analyzed. Among them, 67 patients who received local chemotherapy with cisplatin slow-release polymer after surgical resection were included in the observation group, and the other 70 patients who did not receive chemotherapy after surgical resection were regarded as the control group. The short-term therapeutic efficacy, quality of life score before and after surgery, incidence of toxic and side effects, long-term recurrence rate and survival were compared between the two groups. RESULTS: The total remission rate of clinical treatment in observation group was remarkably higher than that in control group (P<0.05). There was no statistically significant difference in quality of life score between the two groups before and after surgery (P>0.05). There was no significant difference in the incidence of postoperative side effects between the two groups (P>0.05). While the recurrence rates of the observation group at 12 and 24 months after surgery were significantly lower than those in the control group (P<0.05). The overall postoperative survival of observation group was obviously superior to that of control group (P<0.05). In patients who received sustained-release chemotherapy in tumor bed interstitium combined with surgical resection, older ones and the ones with partial surgical resection or pathological grade IV had worse long-term survival (P<0.05). CONCLUSION: The combined treatment of sustained release chemotherapy in tumor bed interstitium and surgical resection for recurrent malignant glioma can effectively improve the clinical efficacy, reduce postoperative recurrence rate and prolong the survival time of the patients.

Androgen is responsible for enhanced susceptibility of melatonin against traumatic brain injury in females.

BACKGROUND: Numerous publications have demonstrated that melatonin administration is associated with mortality reduction and improvement in neurological outcomes after traumatic brain injury (TBI). However, there are significant sex differences in several diseases associated with melatonin. We aimed to determine whether androgen was responsible for enhanced susceptibility of melatonin against TBI in females, as well as potential molecular mechanisms. METHODS: Weight-drop was used to establish a rodent model of TBI. Melatonin (10 mg/kg) and testosterone (1 mg/kg) were administered three times every day for three days after TBI using subcutaneous injection, respectively. Seven days after TBI, an open field assay was used to evaluate locomotor and exploratory activities. Neuronal amount, neuronal apoptosis, and expression of phosphorylated extracellularly regulated protein kinases 1/2 (ERK1/2), c-jun N-terminal kinase 1/2 (JNK1/2), and p38 mitogen-activated protein kinase (p38MAPK) in neurons were assessed using immunofluorescence assay seven days after TBI. The expression of caspase-3, Bax, and Bcl-2 in the frontal cortex was detected using western blot. RESULTS: Compared with female rats, melatonin administration exhibited more neuroprotective effects (including improved locomotor and exploratory activities, elevated neuronal amount, and reduced neuronal apoptosis) in male rats exposed to TBI. Moreover, testosterone significantly improved locomotor and exploratory activities, elevated neuronal amount, decreased neuronal apoptosis, downregulated phosphorylation of JNK1/2- and p38MAPK-positive neurons, but upregulated phosphorylation of ERK1/2-positive neurons in the frontal cortex, and reduced the expressions of cleaved caspase-3, Bax, but increased Bcl-2 expressions in female rats exposed to TBI. CONCLUSIONS: Androgen was responsible for the enhanced susceptibility to TBI under melatonin supplementation in females through a mechanism that may be associated with MAPK pathway regulation.

Long Non-Coding RNA BCAR4 Promotes Growth, Invasion and Tumorigenicity by Targeting miR-2276 to Upregulate MMP7 Expression in Glioma.

OBJECTIVE: Long non-coding RNA breast cancer anti-estrogen resistance 4 (BCAR4) has been recognized as a proto-oncogene in various malignancies. It has been reported to be highly expressed and promote cell proliferation in glioma. However, its additional roles in gliomagenesis remain largely unclear. This research intends to investigate the impact and internal molecular mechanism of BCAR4 on glioma cell growth, invasion and tumorigenesis. METHODS: BCAR4 expression was examined by qPCR in 30 cases of graded glioma specimens and 7 glioblastoma (GBM) cell lines compared with respective controls. Its potential prognostic value was evaluated by Kaplan-Meier survival analysis. The biological roles of BCAR4 in gliomagenesis were verified by CCK-8, transwell and intracranial xenograft assays successively. qPCR and RNA pull-down assays were applied to study the relationship between BCAR4 and miR-2276. Then, qPCR, Western blot and luciferase reporter assays were used to validate the targeting of matrix metallopeptidase 7 (MMP7) by miR-2276 and the regulation of MMP7 by BCAR4. Finally, MMP7 was restored in BCAR4-silenced GBM cells and the rescue effects were determined by CCK-8 and transwell assays. RESULTS: BCAR4 expression was increased in glioma tissues and GBM cell lines, and its high expression positively correlated with advanced grades and worse prognosis. Functional assays verified that knockdown of BCAR4-inhibited cell growth and invasion in vitro, and impaired tumor formation in vivo. Mechanistically, we found that BCAR4 could act as a competing endogenous RNA (ceRNA) by targeting miR-2276 to upregulate MMP7 expression. Importantly, MMP7 restoration effectively rescued the inhibitory modulations on GBM cell growth and invasion caused by BCAR4 knockdown. CONCLUSION: Our findings identified the essential roles of the BCAR4/miR-2276/MMP7 axis in gliomagenesis and provided novel insights on glioma therapy.

Casein Kinase 2 Interacting Protein-1 Suppresses Glioma Cell Proliferation via Regulating the AKT/GSK3ß/ß-Catenin Pathway.

OBJECTIVE: Casein kinase 2 interacting protein-1 (CKIP-1) has exhibited multiple functions in regulating cell proliferation, apoptosis, differentiation, and cytoskeleton. CKIP-1 also plays an important role as a critical regulator in tumorigenesis. The aim of this study is to further examine the function of CKIP-1 in glioma cells. METHODS: The expression level of CKIP-1 protein was determined in gliomas tissues and cell lines by immunohistochemistry stain and western blotting while the association of CKIP-1 expression with prognosis was analyzed by Kaplan-Meier method and compared by log-rank test. CKIP-1 was overexpressed or silenced in gliomas cell lines. CCK-8, colony formation assay, and BrdU incorporation assay were used to determine cell proliferation and DNA synthesis. Cell cycle and apoptosis rate were determined with fluorescence-activated cell sorting (FACS) method. Then, expression of key members in AKT/GSK3ß/ß-catenin pathway was detected by western blot analysis. RESULTS: In the present study, we reported new evidence that CKIP-1 was reversely associated with the proliferation of glioma cells and survival in glioma patients. Additionally, the overexpressed CKIP-1 significantly inhibited glioma cell proliferation. Further experiments revealed that CKIP-1 functioned through its antiproliferative and proapoptotic activity in glioma cells. Importantly, mechanistic investigations suggested that CKIP-1 sharply suppressed the activity of AKT by inhibiting the phosphorylation, markedly downregulated the phosphorylated GSK3ß at Ser9, and promoted ß-catenin degradation. CONCLUSIONS: Overall, our results provided new insights into the clinical significance and molecular mechanism of CKIP-1 in glioma, which indicated CKIP1 might function as a therapeutic target for clinical treatment of glioma.

Antibiotic prophylaxis for infections in patients with acute stroke: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Infections are frequent after stroke and lead to increased mortality and neurological disability. Antibiotic prophylaxis has potential of decreasing the risk of infections and mortality and improving poor functional outcome. Several studies evaluated antibiotic prophylaxis for infections in acute stroke patients have generated conflicting results. The systematic review of randomized clinical trials (RCTs) aimed at comprehensively assessing the evidence of antibiotic prophylaxis for the treatment of acute stroke patients. MATERIALS AND METHODS: PubMed, EMBASE, the Cochrane library and the reference lists of eligible articles were searched to identify all potential studies. We included the studies that investigated the efficacy and safety of antibiotic prophylaxis for the treatment of acute stroke patients. The primary outcome included mortality and infection rate. The secondary outcomes included poor functional outcome and adverse events. RESULTS: Seven trials randomizing 4,261 patients were included. Pooled analyses showed that antibiotic prophylaxis did not improve the mortality (risk ratio (RR) = 1.03, 95% confidence interval (CI) 0.84 to 1.26, p = 0.78, I2 = 25%) and poor functional outcome (RR = 0.93, 95% CI 0.80 to 1.08, p = 0.32, I2 = 80%), but reduced the incidence of infection (RR = 0.67, 95% CI 0.53 to 0.84, p = 0.0007, I2 = 49%). No major side effects were reported. Sensitivity analyses confirmed the results of infection rate and poor functional outcome. CONCLUSIONS: Antibiotic prophylaxis can be used to treat the infectious events of acute stroke patients although it has no potential of decreased mortality and improved functional outcome.

TUSC7 acts as a tumor suppressor in colorectal cancer.

Increasing studies showed that long non-coding RNAs (lncRNAs) played important roles in the development and progression of tumors. Previous evidences suggested that Tumor suppressor candidate 7 (TUSC7) was involved in several tumors initiation. However, the role of TUSC7 in colorectal cancer is still unknown. In this study, we indicated that the expression of TUSC7 was downregulated in colorectal cancer cell lines and tissues. Moreover, the expression of TUSC7 was lower in the high-grade (Dukes C and D) colorectal cancer patients compared to that in the low-grade colorectal cancer patients (Dukes A and B). Colorectal cancer patients with a lower level of TUSC7 expression had worse overall survival rate. Elevated expression of TUSC7 suppressed SW480 and HT29 cell proliferation and invasion. In addition, we demonstrated that overexpression of TUSC7 inhibited the expression of miR-10a and enhanced the expression of PTEN and EphA8, which were the direct target genes of miR-10a. Furthermore, the expression of miR-10a was upregulated in colorectal cancer cell lines and tissues. TUSC7 suppressed colorectal cancer cell proliferation and invasion partly through targeting miR-10a. These results suggested that TUSC7 played as a tumor suppressor gene in colorectal cancer partly through inhibiting miR-10a expression.