Publications by authors named "Qichao Qi"

18 Publications

  • Page 1 of 1

miR-6858 plays a key role in the process of melatonin inhibition of the malignant biological behavior of glioma.

J Clin Neurosci 2021 May 20;87:137-146. Epub 2021 Mar 20.

Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, PR China; Shandong Key Laboratory of Brain Function Remodeling, PR China. Electronic address:

MicroRNAs (miRNAs), small non-coding RNA molecules with a length of 18-25 nucleotides, have been shown to be involved in mediating various malignant properties of GBM, including growth, invasion and angiogenesis. Here, we investigated whether miRNAs might be involved in mediating the suppression of malignant properties of GBM by melatonin (MEL), an amine hormone secreted by the pineal gland. Sequencing was performed to screen specifically for miRNAs induced by MEL in U87 and an orthotopically xenografted primary GBM cell line, GBM#P3. MiR-6858-5p was the most significantly up-regulated miR in GBM cell lines in response to MEL (~5 × ). Transfection of a mimic of miR-6858-5p into both cell lines led to a decrease in viability of ~ 50% at 72 h, confirming a suppressive role for miR-6858-5p in GBM. In contrast, an inhibitor of miR-6858-5p rescued GBM cells from MEL suppression of proliferation, migration and invasion. Analysis using Targetscan yielded candidate mRNAs targeted by miR-6858-5p, some of which are involved in the SIRT/AKT signaling pathway. In cells transfected with a mimic or an inhibitor of miR-6858-5p, levels of SIRT3 and downstream components of the AKT signaling pathway were suppressed or up-regulated, respectively, both in vitro and in an in vivo orthotopic xenograft model. Our results elucidated a novel molecular mechanism underlying MEL suppression of GBM, highlighting a role for miRNAs, and provide a potential therapeutic strategy for GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2021.02.015DOI Listing
May 2021

Deployment of a bioabsorbable plate as the rigid buttress for skull base repair after endoscopic pituitary surgery.

Gland Surg 2021 Mar;10(3):1010-1017

Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China.

Background: Bioresorbable alloplastic implants have become desirable as a rigid buttress for reconstructing skull base defects. This study aimed to describe the use of a biodegradable plate (PolyMax RAPID) in skull base repair of endoscopic endonasal pituitary surgery and to investigate the clinical outcome and safety of this novel method.

Methods: Between January 2019 and January 2020, 22 patients with pituitary adenomas who underwent endoscopic skull base repair with a Polymax RAPID plate were included. After endonasal transsphenoidal surgery, a trimmed bioresorbable plate was placed in the position between the dura and the bone of the skull base to reconstruct the sellar floor and buttress the pituitary gland and sellar packing. The patient demographics, radiologic imaging, and postoperative outcomes were carefully reviewed. All patients were followed up by a routine nasal endoscopic assessment and radiologic examinations.

Results: The present study comprised 10 (45.5%) males and 12 (54.4%) females with an average age of 51.9 years. There were 7 (31.8%) growth hormone (GH) secreting adenomas, 2 (9.1%) thyroid stimulating hormone (TSH) secreting adenomas, and 13 (59.1%) non-functioning adenomas. Enlarged sellar floor and paranasal sinusitis were seen in 13 (59.1%) and 11 (50.0%) cases shown by preoperative computed tomography (CT) or magnetic resonance imaging (MRI), respectively. There were 6 (27.3%) grade-1 and 16 (72.7%) grade-0 cases by intraoperative cerebrospinal fluid (CSF) leak grading. None of these patients received lumbar drains postoperatively and no postoperative CSF rhinorrhea was detected in our series. The PolyMax RAPID plates which could be clearly identified on postoperative CT or sagittal T1-weighted MRI were shown to provide an ideal rigid buttress for sellar repair.

Conclusions: The Polymax RAPID plate can be an optimal implant to achieve rigid repair of sellar floor defects after endonasal transsphenoidal pituitary surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/gs-20-642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033064PMC
March 2021

Rapidly Progressing Honeycomb-Like Germinoma in the Ventricular System.

Ann Neurol 2021 Apr 1. Epub 2021 Apr 1.

Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.26075DOI Listing
April 2021

Glioblastoma Therapy Using Codelivery of Cisplatin and Glutathione Peroxidase Targeting siRNA from Iron Oxide Nanoparticles.

ACS Appl Mater Interfaces 2020 Sep 17;12(39):43408-43421. Epub 2020 Sep 17.

Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, P. R. China.

Glioblastoma (GBM) is the most common and lethal type of malignant brain tumor in adults. Currently, interventions are lacking, the median overall survival of patients with GBM is less than 15 months, and the postoperative recurrence rate is greater than 60%. We proposed an innovative local chemotherapy involving the construction of gene therapy-based iron oxide nanoparticles (IONPs) as a treatment for patients with glioblastoma after surgery that targeted ferroptosis and apoptosis to address these problems. The porous structure of IONPs with attached carboxyl groups was modified for the codelivery of small interfering RNA (siRNA) targeting glutathione peroxidase 4 (si-GPX4) and cisplatin (Pt) with high drug loading efficiencies. The synthesized folate (FA)/Pt-si-GPX4@IONPs exerted substantial effects on glioblastoma in U87MG and P3#GBM cells, but limited effects on normal human astrocytes (NHAs). During intracellular degradation, IONPs significantly increased iron (Fe and Fe) levels, while Pt destroyed nuclear DNA and mitochondrial DNA, leading to apoptosis. Furthermore, IONPs increased HO levels by activating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). The Fenton reaction between Fe, Fe, and intracellular HO generated potent reactive oxygen species (ROS) to initiate ferroptosis, while the co-released si-GPX4 inhibited GPX4 expression and synergistically improved the therapeutic efficacy through a mechanism related to ferroptosis. As a result, superior therapeutic effects with low systemic toxicity were achieved both and , indicating that our nanoformulations might represent safe and efficient ferroptosis and apoptosis inducers for use in combinatorial glioblastoma therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c12042DOI Listing
September 2020

Patients with true mixed growth hormone and prolactin-secreting pituitary adenoma: a case series of 12 patients.

Br J Neurosurg 2020 Apr 24;34(2):154-160. Epub 2020 Jan 24.

Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Mixed growth hormone (GH) and prolactin (PRL) secreting adenomas are the most common type of plurihormonal pituitary adenomas. We assessed the clinical presentations and impacts of transsphenoidal surgery (TS) on patients with mixed GH and PRL adenomas including surgical outcomes, complications, and prognosis. Twelve patients (7 males, 5 females) were operated in the neurosurgery department of Qilu hospital affiliated to Shandong University, Shandong, China. We analyzed hormone levels of preoperation, postoperation (within 24 h) and at 12-month follow-up and correlated levels with tumor volumes. The remission rate was 66.7% (8/12), the recurrence rate was 16.7% (2/12), the cause-specific mortality was 0 and the overall mortality rate was 16.7% (2/12) due to stroke and myocardial infarction respectively. A significant drop was seen in GH, PRL, and Insulin-like-growth-factor-1 (IGF-1) levels between preoperation and postoperation with mean values from 52.6 to 9.9 ng/ml ( = 0.0015), from 321.6 to 190.9 ng/ml ( = 0.0026) and from 815.7 to 230.6 ng/ml ( = 0.0004), respectively. This drop was more significant between preoperation and follow-up with mean values from 52.6 to 3.0 ng/ml ( = 0.002), from 321.6 to 61.6 ng/ml ( < 0.0001), and from 815.7 to 195.0 ng/ml ( = 0.0001), respectively. However, there was no significant correlation between tumor volume and all of the hormone levels. Most mixed GH and PRL adenomas are aggressive with a high risk of recurrence and mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02688697.2020.1713989DOI Listing
April 2020

Reduced expression of proteolipid protein 2 increases ER stress-induced apoptosis and autophagy in glioblastoma.

J Cell Mol Med 2020 03 28;24(5):2847-2856. Epub 2019 Nov 28.

Department of Neurosurgery, Qilu Hospital of Shandong University, Shandong Key Laboratory of Brain Functional Remodeling and Brain Science Research Institute, Shandong University, Shandong, China.

Proteolipid protein 2 (PLP2) is an integral ion channel membrane protein of the endoplasmic reticulum. The protein has been shown to be highly expressed in many cancer types, but its importance in glioma progression is poorly understood. Using publicly available datasets (Rembrandt, TCGA and CGGA), we found that the expression of PLP2 was significantly higher in high-grade gliomas than in low-grade gliomas. We confirmed these results at the protein level through IHC staining of high-grade (n = 56) and low-grade glioma biopsies (n = 16). Kaplan-Meier analysis demonstrated that increased PLP2 expression was associated with poorer patient survival. In functional experiments, siRNA and shRNA PLP2 knockdown induced ER stress and increased apoptosis and autophagy in U87 and U251 glioma cell lines. Inhibition of autophagy with chloroquine augmented apoptotic cell death in U87- and U251-siPLP2 cells. Finally, intracranial xenografts derived from U87- and U251-shPLP2 cells revealed that loss of PLP2 reduced glioma growth in vivo. Our results therefore indicate that increased PLP2 expression promotes GBM growth and that PLP2 represents a potential future therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.14840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077595PMC
March 2020

The Natural Flavonoid Galangin Elicits Apoptosis, Pyroptosis, and Autophagy in Glioblastoma.

Front Oncol 2019 27;9:942. Epub 2019 Sep 27.

Department of Neurosurgery, Qilu Hospital of Shandong University and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.

Galangin (GG), a flavonoid, elicits a potent antitumor activity in diverse cancers. Here, we evaluated the efficacy of GG in the treatment of human glioblastoma multiforme (GBM) and investigated the molecular basis for its inhibitory effects in the disease. GG inhibited viability and proliferation of GBM cells (U251, U87MG, and A172) in a dose-dependent manner (IC = 221.8, 262.5, 273.9 μM, respectively; < 0.001; EdU, ~40% decrease at 150 μM, < 0.001), and the number of colonies formed was significantly reduced (at 50 μM, < 0.001). However, normal human astrocytes were more resistant to its cytotoxic effects (IC >450 μM). Annexin-V/PI staining was increased indicating that GG induced apoptosis in GBM cells (26.67 and 30.42%, U87MG and U251, respectively) and associated proteins including BAX and cleaved PARP-1 were increased (~3×). Cells also underwent pyroptosis as determined under phase-contrast microscopy. Knockdown of gasdermin E (GSDME), a protein involved in pyroptosis, alleviated pyroptosis induced by GG through aggravating nuclear DNA damage in GBM cells. Meanwhile, fluorescent GFP-RFP-MAP1LC3B puncta associated with autophagy increased under GG treatment, and transmission electron microscopy confirmed the formation of autophagic vesicles. Inhibition of autophagy enhanced GG-induced apoptosis and pyroptosis in GBM cells. Finally, in an orthotopic xenograft model in nude mice derived from U87MG cells, treatment with GG in combination with an inhibitor of autophagy, chloroquine, suppressed tumor growth, and enhanced survival compared to GG monotherapy ( < 0.05). Our results demonstrated that GG simultaneously induces apoptosis, pytoptosis, and protective autophagy in GBM cells, indicating that combination treatment of GG with autophagy inhibitors may be an effective therapeutic strategy for GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776614PMC
September 2019

Epithelial membrane protein 1 promotes glioblastoma progression through the PI3K/AKT/mTOR signaling pathway.

Oncol Rep 2019 Aug 19;42(2):605-614. Epub 2019 Jun 19.

Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Key Laboratory of Brain Functional Remodeling, Jinan, Shandong 250012, P.R. China.

Glioblastoma multiforme (GBM) is the most malignant intracranial tumor. Although the affected patients are usually treated with surgery combined with radiotherapy and chemotherapy, the median survival time for GBM patients is still approximately 12‑14 months. Identifying the key molecular mechanisms and targets of GBM development may therefore lead to the development of improved therapies for GBM patients. In the present study, the clinical significance and potential function of epithelial membrane protein 1 (EMP1) in malignant gliomas were investigated. Increased EMP1 expression was associated with increasing tumor grade (P<0.001) and worse prognosis in patients (P<0.001) based on TCGA, Rembrandt and CGGA databases for human gliomas. In vitro, gene silencing of EMP1 in U87MG and P3 GBM (primary glioma) cells significantly inhibited tumor proliferation and invasion. In addition, it was revealed that activation of the PI3K/AKT/mTOR signaling pathway is the driving force of EMP1‑promoted glioma progression. Finally, it was demonstrated, using an intracranial GBM animal model, that EMP1 knockdown significantly inhibits tumor growth in vivo and increases overall survival in tumor‑bearing animals. Our research provides new insights into the molecular mechanisms underlying EMP1 knockdown‑mediated inhibition of GBM cell invasion and raises the possibility that targeting of EMP1 may represent a promising strategy for the treatment of GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2019.7204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609345PMC
August 2019

Matrine induces senescence of human glioblastoma cells through suppression of the IGF1/PI3K/AKT/p27 signaling pathway.

Cancer Med 2018 09 5;7(9):4729-4743. Epub 2018 Aug 5.

Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute, Key Laboratory of Brain Functional Remodeling, Shandong University, Jinan, Shandong, China.

Background: Matrine, a traditional Chinese medicine, has recently been shown to have antitumor properties in diverse cancer cells. Here, we explored the effect of matrine on human glioblastoma multiforme (GBM) cells.

Methods: Glioblastoma multiforme cell lines were treated with matrine to assess proliferation and viability using EdU and CCK8 assays. SA-β-gal assays were used to evaluate cellular senescence, and a cytokine array and ELISA assay were used to screen for secreted cytokines altered in GBM cells after matrine treatment. Immunohistochemistry and Western blot analysis were performed to evaluate protein levels in matrine-treated cell lines and in samples obtained from orthotopic xenografts. Specific activators of AKT and IGF1 were used to identify the pathways mediating the effect.

Results: Matrine potently inhibited growth of GBM cell lines in vitro. Based on in situ assays, growth arrest induced by matrine was primarily achieved through induction of cellular senescence. Matrine treatment led to decreased expression of proteins involved in promoting cell growth, IGF1, PI3K, and pAKT. Exposure of cells to a small molecule activating AKT (SC79) and recombinant IGF1 led to a reduced number of senescent SA-β-gal-positive cells in the presence of matrine. Finally, matrine inhibited growth of orthotopic xenografts established from luciferase-stable-U251 or luciferase-stable-P3 cells and prolonged overall survival in mice.

Conclusions: These results indicated that matrine arrested cell growth through inhibition of IGF1/PI3K/AKT signaling. Matrine warrants further investigation as a potential therapy in the treatment of patients with GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.1720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143938PMC
September 2018

Inhibition of glioma growth by flavokawain B is mediated through endoplasmic reticulum stress induced autophagy.

Autophagy 2018 17;14(11):2007-2022. Epub 2018 Aug 17.

a Department of Neurosurgery , Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Key Laboratory of Brain Functional Remodeling , Jinan , Shandong , P.R. China.

Flavokawain B (FKB), a natural kava chalcone, displays potent antitumor activity in various types of cancer. The mechanism of action, however, remains unclear. Here, we evaluated the efficacy of FKB in the treatment of human glioblastoma multiforme (GBM) as well as the molecular basis for its inhibitory effects in cancer. Approximately 60% of GBM cells became senescent after treatment with FKB as assessed in the senescence-associated (SA)-GLB1/SA-β-galactosidase assay. The cellular process of autophagy potentially contributed to the establishment of senescence. Transmission electron microscopy revealed the formation of autophagic vesicles under FKB treatment, and MAP1LC3B (microtubule associated protein 1 light chain 3 beta)-II was increased. Transfection of ATG5 or ATG7 small interfering RNAs (siRNAs) inhibited FKB-induced autophagy in U251 cells. Western blot revealed that molecular components of the endoplasmic reticulum stress pathway were activated, including ATF4 (activating transcription factor 4) and DDIT3 (DNA damage inducible transcript 3), while levels of TRIB3 (tribbles pseudokinase 3) increased. In addition, based on the phosphorylation status, the AKT-MTOR-RPS6KB1 pathway was inhibited, which induced autophagy in GBM cells. Inhibition of autophagy by autophagy inhibitors 3-methyladenine and chloroquine or knockdown of ATG5 or ATG7 caused FKB-treated U251 cells to switch from senescence to apoptosis. Finally, knockdown of ATG5 or treatment with chloroquine in combination with FKB, significantly inhibited tumor growth in vivo. Our results demonstrated that FKB induced protective autophagy through the ATF4-DDIT3-TRIB3-AKT-MTOR-RPS6KB1 signaling pathway in GBM cells, indicating that the combination treatment of FKB with autophagy inhibitors may potentially be an effective therapeutic strategy for GBM.

Abbreviations: 3-MA: 3-methyladenine; 4-PBA: 4-phenylbutyrate; AKT: AKT serine/threonine kinase; ATF4: activating transcription factor 4; ATG: autophagy related; CASP3: caspase 3; CCK-8: cell counting kit-8; CDKN1A: cyclin-dependent kinase inhibitor 1A; CQ: chloroquine; DDIT3: DNA damage inducible transcript 3; DMEM: Dulbecco's modified Eagle's medium; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; FKB: flavokawain B; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBM: glioblastoma multiforme; GFP: green fluorescent protein; HSPA5: heat shock protein family A (Hsp70) member 5; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; PARP1: poly(ADP-ribose) polymerase; 1RPS6KB1: ribosomal protein S6 kinase B1; SA-GLB1: senescence-associated galactosidase beta 1; siRNA: short interfering RNA; SQSTM1: sequestosome 1; TEM: transmission electron microscopy; TRIB3: tribbles pseudokinase 3; TUNEL: deoxynucleotidyl transferase-mediated dUTP nick-end labeling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2018.1501133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6152528PMC
October 2019

Impact of polymorphisms on glioma risk in Chinese.

Oncotarget 2017 Oct 19;8(48):83712-83722. Epub 2017 Jul 19.

Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan 250012, China.

Several single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGFA) gene have been previously reported to be associated with glioma susceptibility, but individual studies have demonstrated inconclusive results. In the current study, a meta-analysis was performed to derive a more precise estimation of the involvement of polymorphisms in glioma development. A comprehensive literature search conducted in PubMed, Embase, the Cochrane Library, and OVID databases through February 25, 2017 yielded 4 eligible studies consisting of 2,275 cases and 2,475 controls. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated under allele contrast, dominant, recessive, homozygous, and heterozygous models. In general, minor alleles of polymorphisms , , and were associated with increased glioma risk. In contrast, a significant correlation was found between the minor allele of polymorphism and decreased susceptibility to glioma. Moreover, statistically significant associations with glioma risk were observed for polymorphisms and in the meta-analysis although positive associations were not observed in any of the included studies individually. No significant correlations with glioma susceptibility were identified for polymorphisms or except in the recessive model. Finally, stratified analysis on the basis of genotyping method and Hardy-Weinberg equilibrium (HWE) in controls revealed no significant difference between subgroups. Our results indicated that several VEGFA polymorphisms might be risk factors for glioma in Chinese. More studies with larger sample sizes using different ethnicities are needed to provide additional evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.19380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663548PMC
October 2017

Increased NG2 and SOX2 expression is associated with high-grade choroid plexus tumors.

Oncol Lett 2017 Aug 7;14(2):1802-1806. Epub 2017 Jun 7.

Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, P.R. China.

The World Health Organization classification of choroid plexus tumors (CPT) includes three distinct grades: Choroid plexus papilloma (CPP), atypical choroid plexus papilloma (ACPP) and choroid plexus carcinoma (CPC). The molecular basis for these pathological distinctions may help to stratify tumors and provide an insight into the clinical behavior of CPTs. In the present study, the progenitor and stem cell markers neuron glia antigen-2 (NG2) and sex-determining region Y-box 2 (SOX2) were investigated as potential biomarkers that may distinguish between distinct CPT grades. Immunohistochemistry was used to determine the expression of NG2 and SOX2 in CPTs (n=34) from Chinese patients (21 males and 13 females) with a mean age of 31.1 years (range, 1-63 years). The proportion of cells stained were scored using a scale between 0 and 3+, where 0 represents no staining and 3+ represents strong staining, and mean scores for each marker were determined on the basis of tumor grade. Pathological diagnosis revealed a distribution of cases as follows: CPP, 25; ACPP, 5; and CPC, 4. NG2 and SOX2 were expressed in CPTs of all grades. The mean labeling indices for CPP, ACPP and CPC were 1.12, 1.80 and 2.75 for NG2, respectively, and 1.20, 2.00 and 3.00 for SOX2, respectively. Statistical analysis of the mean labeling indices revealed a significant association between the expression of NG2 and SOX2 and CPT grade (P=0.001 and <0.001 for CPP/ACPP and CPP/CPC, respectively). The results of the present study indicated that increased expression of NG2 and SOX2 was associated with higher-grade tumors and that these markers may be useful in determining CPT grade.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2017.6326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529992PMC
August 2017

Associations of five polymorphisms in the CD44 gene with cancer susceptibility in Asians.

Sci Rep 2016 12 21;6:39485. Epub 2016 Dec 21.

Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, #107 Wenhua Xi Road, Jinan, 250012, China.

CD44 polymorphisms have been previously associated with cancer risk. However, the results between independent studies were inconsistent. Here, a meta-analysis was performed to systematically evaluate associations between CD44 polymorphisms and cancer susceptibility. A comprehensive literature search conducted in PubMed, Embase, and Web of Science databases through August 10, 2016 yielded 11 eligible publications consisting of 5,788 cancer patients and 5,852 controls. Overall, odds ratios (OR) calculated with 95% confidence intervals (CI) identified a significant association between CD44 polymorphism rs13347 and cancer susceptibility under all genetic models. Additionally, the minor allele of polymorphism rs11821102 was associated with a decreased susceptibility to cancer in allele contrast, dominant, and heterozygous models, while no significant association was identified for polymorphisms rs10836347, rs713330, or rs1425802. Subgroup analysis by ethnicity revealed rs13347 was significantly associated with cancer susceptibility for Chinese but not for Indians. Linkage disequilibrium (LD) between different polymorphisms varied across diverse ethnic populations. In conclusion, the results indicate that CD44 polymorphism rs13347 acts as a risk factor for cancer, especially in Chinese, while the minor allele of polymorphism rs11821102 may be associated with a decreased susceptibility to cancer. Nevertheless, further studies on a larger population covering different ethnicities are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep39485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5175131PMC
December 2016

Association of HOTAIR polymorphisms rs4759314 and rs920778 with cancer susceptibility on the basis of ethnicity and cancer type.

Oncotarget 2016 Jun;7(25):38775-38784

Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, China.

Polymorphisms in the HOX transcript antisense intergenic RNA (HOTAIR) have been recently associated with susceptibility to different cancers. Here, a meta-analysis was performed to derive a more precise estimation of the involvement of HOTAIR polymorphisms in cancer development. Data from cases (n = 7,772) and controls (n = 9,075) were extracted from eligible studies (n = 10) identified in a comprehensive literature search conducted in PubMed, Embase, and the Web of Science databases through January 20, 2016. Overall, association between polymorphism rs920778 and increased cancer risk was significant in allele contrast (odds ratio (OR) = 1.239, 95% confidence interval (CI) = 1.032 - 1.487) and recessive models (OR = 1.614, 95% CI = 1.082 - 2.406). In subgroup analysis based on ethnicity, a significant association between polymorphism rs920778 and cancer susceptibility was observed in Asians under all models, but was most compelling under recessive (OR = 2.128, 95% CI = 1.417 - 3.197) and homozygous models (OR = 2.764, 95% CI = 2.221 - 3.440). Subgroup analysis by cancer type revealed a significant association between polymorphism rs4759314 and susceptibility to gastric cancer in allele contrast (OR = 1.262, 95% CI = 1.073 - 1.486), dominant (OR = 1.280, 95% CI = 1.060 - 1.547), and heterozygous models (OR = 1.288, 95% CI = 1.057 - 1.570). In conclusion, the results indicated that HOTAIR polymorphism rs920778 was more generally associated with cancer risk, particularly in Asians, while rs4759314 was a risk factor for gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.9608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122428PMC
June 2016

APOBEC3 deletion increases the risk of breast cancer: a meta-analysis.

Oncotarget 2016 Nov;7(46):74979-74986

Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China.

Recently, a deletion in the human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) gene cluster has been associated with a modest increased risk of breast cancer, but studies yielded inconsistent results. Therefore we performed a meta-analysis to derive a more precise conclusion. Six studies including 18241 subjects were identified by searching PubMed and Embase databases from inception to April 2016. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were evaluated under allele contrast, dominant, recessive, homozygous, and heterozygous models. All the analyses suggested a correlation of APOBEC3 deletion with increased breast cancer risk (D vs I: OR = 1.29, 95% CI = 1.23-1.36; D/D+I/D vs I/I: OR = 1.34, 95% CI = 1.26-1.43; D/D vs I/D+ I/I: OR = 1.51, 95% CI = 1.36-1.68; D/D vs I/I: OR = 1.75, 95% CI= 1.56-1.95; I/D vs I/I: OR = 1.28, 95% CI = 1.19-1.36). Stratified analysis by ethnicity showed that the relationship is stronger and more stable in Asians. In summary, our current work indicated that APOBEC3 copy number variations might have a good screening accuracy for breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.11792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342716PMC
November 2016

Berberine induces autophagy in glioblastoma by targeting the AMPK/mTOR/ULK1-pathway.

Oncotarget 2016 Oct;7(41):66944-66958

Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, 250012, P.R. China.

There is an urgent need for new therapeutic strategies for patients with glioblastoma multiforme (GBM). Previous studies have shown that berberine (BBR), a natural plant alkaloid, has potent anti-tumor activity. However, the mechanisms leading to cancer cell death have not been clearly elucidated. In this study, we show that BBR has profound effects on the metabolic state of GBM cells, leading to high autophagy flux and impaired glycolytic capacity. Functionally, these alterations reduce the invasive properties, proliferative potential and induce apoptotic cell death. The molecular alterations preceding these changes are characterized by inhibition of the AMPK/mTOR/ULK1 pathway. Finally, we demonstrate that BBR significantly reduces tumor growth in vivo, demonstrating the potential clinical benefits for autophagy modulating plant alkaloids in cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.11396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341849PMC
October 2016

Nitidine chloride inhibits the malignant behavior of human glioblastoma cells by targeting the PI3K/AKT/mTOR signaling pathway.

Oncol Rep 2016 Oct 3;36(4):2160-8. Epub 2016 Aug 3.

Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Wenhua Xi Road, Jinan, Shandong 250012, P.R. China.

Recent studies have demonstrated that nitidine chloride (NC), a natural bioactive alkaloid, displays potent antitumor activity in various types of cancer. In the present study, NC was examined for efficacy in the treatment of human glioblastoma multiforme (GBM) as well as the molecular basis for its more general inhibitory effects in cancer. U251 and U87 GBM cell lines were exposed to three concentrations of NC (5, 25 and 50 µM) in vitro, and tumor cell growth was assessed on the basis of proliferation, migration and energy metabolism. Decreases in viability and proliferation reached ~50% for both cell lines with 50 µM NC at 24 h as assessed by cell viability Cell Counting Kit-8 (CCK-8) and EdU assays. In wound closure and Transwell assays, migration and invasion were inhibited at 50 µM after 24 h (~20 and 80%, respectively; P<0.05). ATP and L-lactate levels were also decreased after treatment with NC (50 µM, 24 h; P<0.05 and P<0.01, respectively). Finally, in western blot analysis, phosphorylation of Akt and mTOR was suppressed by NC, but partially restored when cells were treated simultaneously with a novel Akt activator, SC79. Partial restoration was also observed in viability/proliferation (U251 and U87, ~15 vs. 40%; NC vs. NC + SC79; P<0.05) and invasion (U251 and U87, ~30 vs. 60%; NC vs. NC + SC79; P<0.05). Our results demonstrated that NC inhibits development of GBM by targeting the PI3K/Akt/mTOR signaling pathway and provides a potential therapeutic agent for the treatment of GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2016.4998DOI Listing
October 2016

Extraventricular Intraparenchymal Choroid Plexus Tumors in Cerebral Hemisphere: A Series of 6 Cases.

World Neurosurg 2015 Dec 11;84(6):1660-7. Epub 2015 Jul 11.

Department of Neurosurgery, Qilu Hospital of Shandong University, Shandong, China; Brain Science Research Institute, Shandong University, Shandong, China. Electronic address:

Objective: Extraventricular intraparenchymal choroid plexus tumors (CPTs) in the cerebral hemisphere are extremely rare. The aim of this study was to investigate the clinical characteristics, radiologic findings, and surgical outcomes of this atypical type of CPT.

Methods: The study comprised 6 patients with pathologically proven extraventricular intraparenchymal CPTs who were surgically treated at Qilu Hospital of Shandong University. The PubMed database was searched for similar cases published before January 2015, and these cases were reviewed.

Results: Patients were 5 (83.3%) men and 1 (16.7%) woman with an average age of 46.5 years. Symptoms and signs of CPT were usually associated with increased intracranial pressure and invasion of functional areas by tumor. Magnetic resonance imaging commonly demonstrated a contrast-enhancing intraparenchymal mass with cysts; hydrocephalus was not observed in any cases. Subtotal resection and gross total resection were achieved in 1 (16.7%) and 5 (83.3%) cases, respectively. There were 3 cases (50.0%) of choroid plexus papilloma, 2 cases (33.3%) of atypical choroid plexus papilloma, and 1 case (16.7%) not otherwise specified. There was a low incidence of postoperative complications, and surgical outcomes of CPTs were satisfactory.

Conclusions: In contrast to typical lesions, extraventricular intraparenchymal CPTs in the cerebral hemisphere are rarely associated with hydrocephalus. Magnetic resonance imaging features are key in preoperative diagnosis; nevertheless, it is difficult to distinguish this atypical type of CPT from other lesions. Surgical removal of the tumor is safe and efficacious.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wneu.2015.07.004DOI Listing
December 2015