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1.
Fish Shellfish Immunol ; 141: 109092, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37722441

ABSTRACT

CD46, as a cofactor of complement I factor, not only regulates the complement system but also functions as a pathogen receptor and is involved in controlling early pathogen infection through autophagy. In this study, a new CD46 gene (ToCD46) was identified from golden pompano (Trachinotus ovatus), which showed higher sequence homology with other teleosts CD46. Homology comparison showed that ToCD46 had higher sequence homology (46.95-52.85%) with other teleosts CD46 and lower homology with mammal. Tissue expression profile analysis showed that ToCD46 was generally expressed in all tissues with the highest expression level in liver, followed by head kidney, and showed different patterns of up-regulation in immune-related tissues after stimulation by Streptococcus agalactiae and Vibrio alginolyticus. The hemolytic activity analysis and apoptosis assay showed that rToCD46 decreased the hemolytic activity of serum of golden pompano and effectively inhibited the damage of A549 cells, suggesting that ToCD46 might be involved in the regulation of complement activation of golden pompano. In vitro antibacterial experiments showed that rToCD46 had antibacterial activity against gram negative bacteria V. alginolyticus but no effect on positive bacteria S. agalactiae. These results suggest that ToCD46 may be involved in the immune response of golden pompano to pathogens, which will provide important basic information for elucidating the evolutionary history of the complement system of golden pompano.


Subject(s)
Anti-Infective Agents , Perciformes , Vibrio Infections , Animals , Immunity, Innate/genetics , Vibrio Infections/veterinary , Fishes , Complement System Proteins , Immunologic Factors , Anti-Bacterial Agents , Fish Proteins , Mammals/metabolism
2.
Int J Clin Pharmacol Ther ; 61(10): 423-429, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37548453

ABSTRACT

OBJECTIVE: To determine the therapeutic effects of lenvatinib combined with bevacizumab following transarterial chemoembolization (TACE) in patients with primary liver cancer. MATERIALS AND METHODS: 100 patients with primary liver cancer were recruited in the period from January 2020 to January 2021 and allocated with randomization into a control group (n = 50) and a test (bevacizumab) group (n = 50). The patients in the control group received lenvatinib for 4 weeks following TACE, whereas those in the test group received bevacizumab for 6 weeks prior to TACE and subsequent therapy with lenvatinib for 4 weeks. The serum concentration of interferon-γ (INF-γ), interleukin-10 (IL-10), soluble interleukin-2 receptor (sIL-2R), interleukin-12 (IL-12), superoxide dismutase (SOD), total antioxidant capacity (TAOC), glutathione (GSH), malondialdehyde (MDA), total bilirubin (TBil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), carbohydrate antigen 242 (CA242), CA724, α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) were determined in both groups at the commencement of treatment in January 2020 and 12 months later and compared with the observed therapeutic effects. RESULTS: The concentrations of CA242, CEA, CA724, and AFP in the bevacizumab group were lower than those in the control group (p < 0.05). The concentration of IL-12 and INF-γ in the bevacizumab group were higher, but the levels of IL-10 and sIL-2R lower than in the control group (p < 0.05). In the bevacizumab group, the level of MDA was lower, whereas the levels of TAOC, SOD, and GSH were higher than those in the control group (p < 0.05). The bevacizumab group also had lower levels of ALT, TBil, and AST and a higher level of ALP than control group (p < 0.05). The response rate based on tumor status (size, progression) in the bevacizumab group was higher than in the control group (p < 0.05). CONCLUSION: The therapeutic effects of lenvatinib following TACE in primary liver cancer are significantly greater when combined with bevacizumab administered for 6 weeks prior to TACE.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Bevacizumab/adverse effects , alpha-Fetoproteins/therapeutic use , Interleukin-10/therapeutic use , Carcinoembryonic Antigen/therapeutic use , Chemoembolization, Therapeutic/adverse effects , Interleukin-12/therapeutic use , Superoxide Dismutase , Treatment Outcome
3.
Appl Bionics Biomech ; 2022: 8931131, 2022.
Article in English | MEDLINE | ID: mdl-35465182

ABSTRACT

More and more people are beginning to recognize the important role of intelligent rehabilitation training equipment in rehabilitation treatment and continue to carry out related researches. The use of intelligent robot technology for rehabilitation treatment has been rapidly developed, and it has achieved rapid progress on a global scale. Especially in some developed countries, this field has also received corresponding attention in some developed cities in China in recent years. Mesoporous nanomaterials have unique physical, chemical, and biological properties. Mesoporous nanomaterials can be combined with chemotherapy drugs to minimize the harm caused by chemotherapy drugs to the human body and improve the therapeutic effect. As a result, the cure rate has been improved, and it has shown deep potential in breast cancer chemotherapy. Fifty breast cancer patients were selected as the research objects and randomly divided into a control group and an experimental group, each with 25 cases. The control group was treated with conventional chemotherapeutics, and the experimental group was treated with molecular targeted therapy to compare the treatment effects of the two groups. Studies have shown that the recurrence rate and the occurrence probability of complications in the experimental group are significantly lower than those in the control group. Molecular targeted therapy for breast cancer has obvious effects, which reduces the recurrence rate of complications or diseases, and is less toxic.

4.
Biomaterials ; 34(35): 8968-78, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23953782

ABSTRACT

The application of carmustine (BCNU) for glioma treatment is limited due to its poor selectivity for tumor and tumor resistance caused by O6-methylguanine-DNA-methyl transferase (MGMT). To improve the efficacy of BCNU, we constructed chitosan surface-modified poly (lactide-co-glycolides) nanoparticles (PLGA/CS NPs) for targeting glioma, loading BCNU along with O6-benzylguanine (BG), which could directly deplete MGMT. With core-shell structure, PLGA/CS NPs in the diameter around 177 nm showed positive zeta potential. In vitro plasma stability of BCNU in NPs was improved compared with free BCNU. The cellular uptake of NPs increased with surface modification of CS and decreasing particle size. The cytotoxicity of BCNU against glioblastoma cells was enhanced after being encapsulated into NPs; furthermore, with the co-encapsulation of BCNU and BG into NPs, BCNU + BG PLGA/CS NPs showed the strongest inhibiting ability. Compared to free drugs, PLGA/CS NPs could prolong circulation time and enhance accumulation in tumor and brain. Among all treatment groups, F98 glioma-bearing rats treated with BCNU + BG PLGA/CS NPs showed the longest survival time and the smallest tumor size. The studies suggested that the co-encapsulation of BCNU and BG into PLGA/CS NPs could remarkably enhance the efficacy of BCNU, accompanied with greater convenience for therapy.


Subject(s)
Carmustine/pharmacokinetics , Cations/chemistry , Glioblastoma/drug therapy , Nanoparticles/chemistry , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/chemistry , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Carmustine/chemistry , Cell Line, Tumor , Chemical Phenomena , Disease Models, Animal , Drug Delivery Systems , Female , Guanine/analogs & derivatives , Guanine/chemistry , Guanine/pharmacokinetics , Magnetic Resonance Imaging , Male , Rats , Rats, Inbred F344
5.
Int J Clin Exp Pathol ; 6(5): 878-88, 2013.
Article in English | MEDLINE | ID: mdl-23638219

ABSTRACT

Papillary meningioma is a rare subtype of malignant meningiomas, which is classified by the World Health Organization as Grade III. Because of lack of large sample size case studies, many of the specific characteristics of papillary meningioma are unclear. This study investigated by retrospective analysis the clinical, radiological and histopathological findings of 17 papillary meningioma patients who underwent surgical resection or biopsy, to assess the characteristics of papillary meningioma. Eight female and nine male patients were included, with a mean age of 40 (range: 6 to 55) years. Tumors were mostly located in the cerebral convexity and showed irregular margins, absence of a peritumoral rim, heterogeneous enhancement and severe peritumoral brain edema on preoperative images. Brain invasion was often confirmed during the operations, with abundant to exceedingly abundant blood supply. Intratumoral necrosis and mitosis was frequently observed on routinely stained sections. The average MIB-1 labeling index was 6.9%. Seven cases experienced tumor recurrence or progression, while seven patients died 6 to 29 months after operation. Radiation therapy was given in 52.9% of all cases. Univariate analysis showed that only the existence of intratumoral necrosis and incomplete resection correlated with tumor recurrence. The 3-year progression free survival was 66.7% after gross total resection and 63.6% for other cases. The 3-year mortality rate was 50% after gross total resection and 63.6% for other cases. Papillary meningioma has specific clinical and histopathological characteristics. Tumor recurrence (or progression) and mortality are common. Gross total tumor resection resulted in less recurrence and mortality.


Subject(s)
Meningeal Neoplasms/pathology , Meningioma/pathology , Adolescent , Adult , Child , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Meningeal Neoplasms/mortality , Meningeal Neoplasms/therapy , Meningioma/mortality , Meningioma/therapy , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neurosurgical Procedures , Prognosis , Radiotherapy , Retrospective Studies , Young Adult
6.
Tumour Biol ; 34(4): 2283-92, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23589055

ABSTRACT

Glioma is the most common primary brain tumor, yet the high cost of diagnostic imaging has made early detection of asymptomatic glioma a formidable challenge. Thus, the development of a convenient, sensitive, and cost-effective diagnostic strategy, such as enzyme-linked immunosorbent assay (ELISA) based on glioma-specific and World Health Organization (WHO) grade-specific autoantibody serum markers, is necessary. To this end, a comparative proteomic analysis based on two-dimensional western blotting was carried out with the sera of glioma patients and normal controls. Of the 11 novel glioma-expressed autoantibodies, the autoantibody against glial fibrillary acidic protein (GFAP) showed the highest differential expression. To investigate the potential clinical utility of the GFAP autoantibody as an early diagnostic marker for glioma, an ELISA-based assay was developed and validated with sera from glioma patients with WHO grades II (n = 19), III (n = 17), and IV (n = 24). The GFAP autoantibody level directly correlated with WHO grade and tumor volume. Sera from patients of non-glioma brain tumors, as well as non-brain tumors, showed much lower levels of GFAP autoantibody than those of the glioma patients, indicating that elevated GFAP autoantibody is specific to glioma patients. Analysis of the receiver operating characteristics curve suggested that the new ELISA has good distinguishing power and sensitivity for diagnosing glioma patients. This is the first ELISA assay developed for an autoantibody of a glioma antigen and may prove valuable for the clinical detection of glioma.


Subject(s)
Autoantibodies/blood , Biomarkers, Tumor/immunology , Brain Neoplasms/diagnosis , Brain Neoplasms/immunology , Glial Fibrillary Acidic Protein/immunology , Glioma/diagnosis , Glioma/immunology , Autoantibodies/immunology , Biomarkers, Tumor/blood , Brain Neoplasms/blood , Enzyme-Linked Immunosorbent Assay , Glioma/blood , Humans
7.
Clin Neurol Neurosurg ; 115(8): 1407-14, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23485253

ABSTRACT

OBJECTIVE: To discuss the clinical characteristics, radiological features, surgical treatment and prognosis of sporadic meningioangiomatosis (MA). METHODS: We retrospectively analyzed the medical records of ten histopathologically confirmed MA patients who were treated in the Department of Neurosurgery of Huashan hospital from 2002 to 2011. All of the patients presented with symptomatic seizure attacks before craniotomy surgeries. Magnetic resonance imaging (MRI) and/or computed tomography (CT) were the main radiological examination for preoperative diagnosis of all cases. RESULTS: All patients underwent craniotomy surgeries with gross total resections (GTRs) of the MA lesions. Postoperative follow-ups range from 8 to 108 months, in average 42.7 months, median 40.5 months. No radiological recurrence can be found in any case. Eight patients (80.0%) have achieved total symptomatic remission after surgeries (one of them underwent delayed remission), while two (20.0%) are still suffering from seizure attacks infrequently under several antiepileptic drugs (AEDs). CONCLUSION: Although MA cases are quite rare and usually misdiagnosed presurgically, a correct preoperative diagnosis, at least a differential diagnosis, can be rationally achieved via a triad of patients' ages, symptomatic seizure attacks and radiological features (both CT and MR). MA is curable and the prognosis is excellent since most patients became free of seizure and recurrence after surgical treatments.


Subject(s)
Meningioma/diagnosis , Meningioma/surgery , Neurosurgical Procedures/methods , Adolescent , Adult , Age of Onset , Child , Child, Preschool , Craniotomy , Female , Follow-Up Studies , Humans , Immunohistochemistry , Infant , Magnetic Resonance Imaging , Male , Meningioma/diagnostic imaging , Movement Disorders/etiology , Seizures/etiology , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
8.
Int J Clin Exp Pathol ; 6(3): 358-74, 2013.
Article in English | MEDLINE | ID: mdl-23412548

ABSTRACT

Secretory meningioma (SM) is a rare, benign subtype of meningioma. Between January 2005 and December 2010, 70 SMs were operated on at the Department of Neurosurgery, Huashan Hospital, Fudan University. We retrospectively analyzed the clinical data, radiological and immunohistochemical findings, and patient outcome to discuss the specific features of SMs. Cranial base preference, hyper-signal in T2 weighted MR image, "xenon light" gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement were frequently observed in the 70 cases. Non-skull base SMs, which received more complete resection (p<0.01) and had better short-term and long-term outcome, were observed with more severe peritumoral brain edema (PTBE) (p<0.001). In follow-up, only 1 cranial base SM case showed tumor progression. 3 cases died after operation, all with cranial base SMs. As for the 10 cases given Simpson grade 3 or 4 resection who were available at follow-up, 3 died, 5 received gamma-knife therapy, and the other 2 cases received no treatment at all. Only one of the 2 residual SMs without postoperative radiation presented minor progression at a median of 48 months follow-up. In conclusion, cranial base preference, hyper-signal T2 weighted MR image and "xenon light" GD-DTPA enhancement are specific for SMs. Prognosis of SMs is related with operation completeness and surgical risks, rather than the extent of PTBE. Residual SM grows slowly and reacts well to gamma-knife therapy.


Subject(s)
Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/pathology , Meningioma/diagnostic imaging , Meningioma/pathology , Radiography/methods , Adult , Aged , Disease Progression , Female , Humans , Magnetic Resonance Imaging , Male , Meningeal Neoplasms/surgery , Meningioma/surgery , Middle Aged , Prognosis , Radiosurgery , Retrospective Studies
9.
Chin Med J (Engl) ; 126(3): 488-93, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23422112

ABSTRACT

BACKGROUND: Meningioma is one of the most common primary tumors of the central nervous system, but there are not many detailed studies on the sex, age, subtypes and locations of large series. This study was a retrospective analysis of the characteristics of meningioma cases consecutively operated on at a single institution in China from 2001 to 2010. METHODS: This study investigated the demographic background of 7084 meningioma cases, and the subtypes and locations of the tumors. Sex and age distributions were analyzed, and the pathological subtypes were classified according to the World Health Organization (WHO) classification. The location of the meningiomas was also categorized. RESULTS: The female:male ratio of the 7084 cases was 2.34:1. The mean age was 51.4 years (range, 11 months-86 years). The mean age of cases of WHO grade I meningioma was significantly older than that of grade II or III meningiomas (P < 0.001, Fisher's Least Significant Digit test). There was a significantly higher female:male ratio in WHO grade I meningiomas than in grade II or grade III meningiomas (2.57, 1.03 and 0.76, respectively; P < 0.001, χ(2) test). Meningothelial (n = 2061) and fibrous meningiomas (n = 3556) were the most common subtypes, comprising 79.3% of all meningiomas. All meningioma cases were classified into 23 locations in this study, with the cerebral convexity the most common site (38.33%, n = 2722). Cases with uncommon locations such as extra-cranial and sylvian fissure meningiomas were also present in this series. CONCLUSIONS: Female predominance was found for benign meningiomas, while malignant subtypes showed male predominance. The mean age of patients with WHO grade I meningiomas was older than that of patients with higher-grade tumors. Meningothelial and fibrous meningiomas were the most common subtypes. The cerebral convexity was the most common meningioma location.


Subject(s)
Meningioma/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Middle Aged , Sex Distribution , Young Adult
11.
World Neurosurg ; 79(5-6): 724-32, 2013.
Article in English | MEDLINE | ID: mdl-22902360

ABSTRACT

BACKGROUND: Rhabdoid meningioma (RM) is a rare subtype of meningioma, classified as World Health Organization grade III with a poor prognosis. Here we present our experience on RM and review relevant literature in an attempt to investigate the clinical features, treatment, and prognosis of these tumors. METHODS: Twelve patients underwent surgical treatment for intracranial RMs between 2003 and 2008 in our department. The clinical data, radiological manifestations, pathological findings, treatments, and prognoses of the patients were analyzed retrospectively; 58 other cases reported previously by other institutions also were summarized and reviewed. RESULTS: These cases (6 men and 6 women, mean age 44.3 years old, ranging from 21 to 78 years old) constituted 0.28% of all meningioma patients admitted at our department during the same period. The mean duration of symptoms was relatively short at 1.6 months. There was no significant clinical manifestation noted, and the radiologic findings fell into 3 types of images. In the follow-up period of over 30 months, 7 patients died; 5 patients had recurrence and 2 patients died of unknown causes. CONCLUSIONS: RM is a rare subtype of malignant meningioma featuring an increased tendency for recurrence and possible metastasis. It is still difficult to make a correct preoperative diagnosis. The overall prognosis for these patients is extremely poor, and the role of various adjuvant treatments needs to be further studied.


Subject(s)
Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/surgery , Meningioma/diagnosis , Meningioma/surgery , Adult , Aged , Female , Humans , Magnetic Resonance Imaging , Male , Meningeal Neoplasms/mortality , Meningeal Neoplasms/pathology , Meningioma/mortality , Meningioma/pathology , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Postoperative Complications/diagnosis , Postoperative Complications/mortality , Prognosis , Reoperation , Retrospective Studies , Survival Analysis , Young Adult
12.
Phys Med Biol ; 57(24): 8393-404, 2012 Dec 21.
Article in English | MEDLINE | ID: mdl-23202049

ABSTRACT

Glioma is the primary tumor in the central nervous system, and poses one of the greatest challenges in clinical treatment. MIB-1 and p53 are the most useful biomarkers for gliomas and could help neurosurgeons establish a therapeutic schedule. However, these biomarkers are commonly detected with the help of immunohistochemistry (IHC), which wastes time and energy and is often influenced by subjective factors. To reduce the subjective factors and improve the efficiency in the judgment of IHC, a novel magnetic resonance image (MRI) analysis method is proposed in the present study to detect the expression status of MIB-1 and p53 in IHC. The proposed method includes two kinds of MRI acquisition (FLAIR and T1 FLAIR images), regions of interest (ROIs) selection, texture features (i.e. the gray level gradient co-occurrence matrix (GLGCM), Minkowski functions (MFs), etc) extraction in ROIs, and classification with a support vector machine in a leave-one-out cross validation strategy. By classifying the ROIs, the performance of the method was evaluated by accuracy, area under ROC curve (AUC), etc. A high accuracy (0.7640 ± 0.0225) and AUC (0.7873 ± 0.0377) for MIB-I detection were achieved. In terms of the texture features, 0.7621 ± 0.0199, 0.7666 ± 0.0365 and 0.7426 ± 0.0451 AUC can be obtained using only GLCM, RLM or GLGCM for MIB-1 detection, respectively. In all, the experimental results demonstrated that MR image texture features are associated with the expression status of MIB-1 and p53. The proposed method has the potential to realize high accuracy and robust detection for MIB-I expression status, which makes it promising for clinical glioma diagnosis and prognosis.


Subject(s)
Glioma/diagnosis , Glioma/metabolism , Image Processing, Computer-Assisted/methods , Ki-67 Antigen/metabolism , Magnetic Resonance Imaging/methods , Tumor Suppressor Protein p53/metabolism , Adolescent , Adult , Aged , Brain Neoplasms/diagnosis , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Glioma/pathology , Humans , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Support Vector Machine , Young Adult
13.
Chin Med J (Engl) ; 125(24): 4328-33, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23253696

ABSTRACT

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) dates back to the 1990s and has been successfully applied in neurosurgery but they were low-field iMRI (< 1.0T). This paper reports the clinical experience with a 3T iMRI-integrated neurosurgical suite in Huashan Hospital, Shanghai, China. METHODS: From September 2010 through March 2012, 373 consecutive patients underwent neurological surgery under guidance with 3T iMRI. A retrospective analysis was conducted regarding clinical efficiency. RESULTS: All surgery in the 373 patients was safe. The ratio of gross total resection for cerebral gliomas (n = 161) was increased from 55.90% to 87.58%. The ratio of benefit in extent of resection was 39.13%. One hundred and fifty eight of the 161 glioma patients accomplished follow-up at 3 months postoperatively. Twenty of 161 patients (12.42%) suffered from early motor deficit after surgery. Late motor deficit was however observed in five of 158 patients (3.16%). Twenty-one of 161 patients (13.04%) had early speech deficit and late speech deficit was only observed in six of 158 patients (3.80%). The ratio of gross total resection for pituitary adenomas (n = 49) was increased from 77.55% to 85.71%. The ratio of benefit in extent of resection was 10.2%. There were no iMRI-related adverse events even for patients who underwent awake craniotomy. CONCLUSION: The 3T iMRI integrated neurosurgical suite provides high-quality intraoperative structural and functional imaging for real-time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery.


Subject(s)
Magnetic Resonance Imaging/methods , Neurosurgical Procedures/methods , Adolescent , Adult , Aged , Brain Neoplasms/surgery , Child , Child, Preschool , China , Female , Glioma/surgery , Humans , Male , Middle Aged , Young Adult
14.
J Proteomics ; 77: 480-91, 2012 Dec 21.
Article in English | MEDLINE | ID: mdl-23041135

ABSTRACT

The oligodendroglioma (OG) type of glial cell tumors accounts for 2-5% of primary brain neoplasms and 4-15% of gliomas diagnosed worldwide. Allelic losses on 1p, or on 1p and 19q, correlate with chemotherapy response and good prognosis in OG patients; however, the underlying mechanisms are not yet clearly defined. Therefore, we utilized a quantitative proteomics strategy that combined 8-plex isobaric tags for relative and absolute quantitation (iTRAQ) labeling and two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC/MS/MS) to identify molecular signatures, reveal mechanisms, and develop predictive markers of OG patients with 1p loss of heterozygosity (LOH). An initial screening of four OG patients with 1p LOH and four without were identified, and 449 differentially expressed proteins were quantified, 13 of which were significantly different between the two groups. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway suggested that 1p LOH may affect the actin network in OG. The differential expression of four of the 13 candidates (UBA1, ubiquitin-like modifier activating enzyme 1; ATP6V1E1, ATPase, H+ transporting, lysosomal 31 kDa, V1 subunit E1; MAP2, microtubule-associated protein 2; and HMGB1, high-mobility group protein B1) was validated in 39 additional OG samples using immunohistochemistry. Decision tree modeling indicated that MAP2 expression is a powerful predictor of 1p LOH. Our results not only demonstrate the utility of iTRAQ-based high-throughput quantitative proteomic analysis in glioma research, but also provide novel markers that may help to reveal the mechanisms of 1p LOH-associated chemosensitivity, and to design diagnostic and prognostic assays and therapeutics for OG.


Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/metabolism , Chromosomes, Human, Pair 1 , Loss of Heterozygosity , Neoplasm Proteins/metabolism , Nerve Tissue Proteins/metabolism , Oligodendroglioma/metabolism , Biomarkers, Tumor/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Chromosomes, Human, Pair 19 , Female , Humans , Male , Neoplasm Proteins/genetics , Nerve Tissue Proteins/genetics , Oligodendroglioma/drug therapy , Oligodendroglioma/genetics , Oligodendroglioma/pathology , Proteomics/methods
15.
Biomaterials ; 33(32): 8062-74, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22884813

ABSTRACT

Small-diameter synthetic vascular grafts have high failure rate and tissue-engineered blood vessels are limited by the scalability. Here we engineered bioactive materials for in situ vascular tissue engineering, which recruits two types of endogenous progenitor cells for the regeneration of blood vessels. Heparin was conjugated to microfibrous vascular grafts to suppress thrombogenic responses, and stromal cell-derived factor-1α (SDF-1α) was immobilized onto heparin to recruit endogenous progenitor cells. Heparin-bound SDF-1α was more stable than adsorbed SDF-1α under both static and flow conditions. Microfibrous grafts were implanted in rats by anastomosis to test the functional performance. Heparin coating improved the short-term patency, and immobilized SDF-1α further improved the long-term patency. SDF-1α effectively recruited endothelial progenitor cells (EPCs) to the luminal surface of the grafts, which differentiated into endothelial cells (ECs) and accelerated endothelialization. More interestingly, SDF-1α increased the recruitment of smooth muscle progenitor cells (SMPCs) to the grafts, and SMPCs differentiated into smooth muscle cells (SMCs) in vivo and in vitro. Consistently, SDF-1α-immobilized grafts had significantly higher elastic modulus. This work demonstrates the feasibility of simultaneously recruiting progenitor cells of ECs and SMCs for in situ blood vessel regeneration. This in situ tissue engineering approach will have broad applications in regenerative medicine.


Subject(s)
Anticoagulants/pharmacology , Blood Vessel Prosthesis , Chemokine CXCL12/pharmacology , Endothelial Cells/drug effects , Heparin/pharmacology , Myocytes, Smooth Muscle/drug effects , Stem Cells/drug effects , Animals , Anticoagulants/administration & dosage , Cell Differentiation/drug effects , Cells, Cultured , Chemokine CXCL12/administration & dosage , Coated Materials, Biocompatible/chemistry , Elastic Modulus , Endothelial Cells/cytology , Heparin/administration & dosage , Male , Myocytes, Smooth Muscle/cytology , Rats , Rats, Sprague-Dawley , Stem Cells/cytology , Vascular Grafting , Vascular Patency/drug effects
16.
Acta Neurochir (Wien) ; 154(8): 1361-70; discussion 1370, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22729482

ABSTRACT

BACKGROUND: The marginal delineation of gliomas cannot be defined by conventional imaging due to their infiltrative growth pattern. Here we investigate the relationship between changes in glioma metabolism by proton magnetic resonance spectroscopic imaging ((1)H-MRSI) and histopathological findings in order to determine an optimal threshold value of choline/N-acetyl-aspartate (Cho/NAA) that can be used to define the extent of glioma spread. METHOD: Eighteen patients with different grades of glioma were examined using (1)H-MRSI. Needle biopsies were performed under the guidance of neuronavigation prior to craniotomy. Intraoperative magnetic resonance imaging (MRI) was performed to evaluate the accuracy of sampling. Haematoxylin and eosin, and immunohistochemical staining with IDH1, MIB-1, p53, CD34 and glial fibrillary acidic protein (GFAP) antibodies were performed on all samples. Logistic regression analysis was used to determine the relationship between Cho/NAA and MIB-1, p53, CD34, and the degree of tumour infiltration. The clinical threshold ratio distinguishing tumour tissue in high-grade (grades III and IV) glioma (HGG) and low-grade (grade II) glioma (LGG) was calculated. RESULTS: In HGG, higher Cho/NAA ratios were associated with a greater probability of higher MIB-1 counts, stronger CD34 expression, and tumour infiltration. Ratio threshold values of 0.5, 1.0, 1.5 and 2.0 appeared to predict the specimens containing the tumour with respective probabilities of 0.38, 0.60, 0.79, 0.90 in HGG and 0.16, 0.39, 0.67, 0.87 in LGG. CONCLUSIONS: HGG and LGG exhibit different spectroscopic patterns. Using (1)H-MRSI to guide the extent of resection has the potential to improve the clinical outcome of glioma surgery.


Subject(s)
Aspartic Acid/analogs & derivatives , Brain Neoplasms/metabolism , Choline/metabolism , Glioma/metabolism , Adolescent , Adult , Aged , Aspartic Acid/metabolism , Biopsy, Needle , Brain Neoplasms/pathology , Female , Glioma/pathology , Humans , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Male , Middle Aged , Young Adult
17.
Int J Cancer ; 130(2): 309-18, 2012 Jan 15.
Article in English | MEDLINE | ID: mdl-21328340

ABSTRACT

Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ), has demonstrated promising activity against gliomas, the effects last only a few months and drug resistance develops thereafter in many cases. It has been acknowledged that glioma cells respond to TMZ treatment by undergoing G2/M arrest, but not apoptosis. Here we demonstrate a phase-specific chemotherapy resistance due to cellular prion protein (PrPc) in human glioma cells upon TMZ treatment. TMZ-induced G2/M-arrested cultures show an upregulation of PrPc expression and are more resistant, whereas G1/S-phase cells that show decreased levels of PrPc are more sensitive to apoptosis. Furthermore, an investigation into the biological significance of PrPc association with par-4 provided the first evidence of a relationship between the endogenous levels of PrPc and the resistance of glioma cells to the apoptotic effects of TMZ. Upon TMZ treatment, PrPc exerts its antiapoptotic activity by inhibiting PKA-mediated par-4 phosphorylation that are important for par-4 activation, nuclear entry and initiation of apoptosis. In context with cell cycle-dependent responses to chemotherapy, the data from this study suggest the possibility of exploiting the PrPc-dependent pathway to improve the efficacy of TMZ-based regimen for patients with gliomas.


Subject(s)
Antineoplastic Agents, Alkylating/pharmacology , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Dacarbazine/analogs & derivatives , Glioma/metabolism , Glioma/pathology , PrPC Proteins/metabolism , Receptors, Thrombin/metabolism , Animals , Apoptosis/drug effects , Brain Neoplasms/drug therapy , Cell Cycle/drug effects , Cell Cycle/physiology , Cell Line, Tumor , Cyclic AMP-Dependent Protein Kinases/metabolism , Dacarbazine/pharmacology , Drug Resistance, Neoplasm , Female , Glioma/drug therapy , Humans , Mice , Mice, Inbred NOD , Mice, SCID , Phosphorylation , PrPC Proteins/antagonists & inhibitors , PrPC Proteins/biosynthesis , PrPC Proteins/genetics , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Receptors, Thrombin/antagonists & inhibitors , Receptors, Thrombin/biosynthesis , Receptors, Thrombin/genetics , Temozolomide , Transfection
18.
Zhonghua Wai Ke Za Zhi ; 49(8): 683-7, 2011 Aug 01.
Article in Chinese | MEDLINE | ID: mdl-22168929

ABSTRACT

OBJECTIVE: To report the preliminary experience in clinical application of 3.0 T intraoperative magnetic resonance imaging (iMRI) neuronavigation system in China. METHODS: From September 2010 to March 2011, a consecutive series of 122 patients with intracranial lesions underwent operations in guidance with 3.0 T iMRI. A retrospective analysis was conducted regarding clinical efficiency. RESULTS: Among 122 procedures, the numbers of intraoperative scanning were 2 - 4 times with an average of 2.6. The qualities of images were excellent. Due to the discovery and further possibility of resection of residual tumors, the ratio of gross total resection was increased from 71.7% to 90.0% in cerebral gliomas (n = 60), while from 75.9% to 93.1% in macroadenomas (n = 29). There were 6.7% of all patients occurred postoperative paralysis, but only 3.3% of patients had persistent paralysis at 1 - 2 months follow-up. There was no iMRI-related adverse event occurred. During the same period, more than 2500 patients underwent diagnostic MRI scanning. CONCLUSIONS: 3.0 T iMRI neuronavigation system provides high-quality intraoperative structural, functional and metabolic images for real time tumor resection control and accurate functional preservation, resulting in an improvement in maximal safe brain surgery. The system is cost-effective.


Subject(s)
Magnetic Resonance Imaging , Neuronavigation/methods , Adolescent , Adult , Aged , Brain Neoplasms/surgery , Child , Female , Glioma/surgery , Humans , Male , Middle Aged , Pituitary Neoplasms/surgery , Retrospective Studies , Young Adult
19.
Int J Cancer ; 128(1): 166-75, 2011 Jan 01.
Article in English | MEDLINE | ID: mdl-20209496

ABSTRACT

Vascular endothelial growth factor A (VEGFA), one of the most predominant mediators of pathologic angiogenesis, plays a critical role in glioma carcinogenesis and development via promoting tumor growth. We hypothesized that VEGFA polymorphisms may influence glioma risk. We recently genotyped 9 VEGFA single-nucleotide polymorphisms (SNPs) in 766 glioma patients and 824 cancer-free controls selected from a Chinese population. We evaluated the glioma risk conferred by individual SNPs, haplotypes as well as cumulative SNP effect. In the single-locus analysis, we found that rs2010963 (G+405C, G-634C) [odds ratio (OR) = 1.29; 95% confidence interval (CI) = 1.04-1.58; GC/CC vs. GG] and rs3025030 (OR = 2.21; 95% CI = 1.18-4.14; CC vs. GG/GC) were associated with increased risk for glioma, and rs3024994 (OR = 0.66; 95% CI = 0.47-0.94; CT/TT vs. CC) was associated with reduced glioma risk, albeit insignificant after Bonferroni correction for multiple comparisons. The haplotype-based analysis revealed that AGG in block 1 and ATT, ACT in block 2 were associated with 20-40% reductions in glioma risk. The inverse association of haplotype AGG containing rs2010963G remained significant after correction for multiple testing (p = 0.002, p(corrected) = 0.022). The aforementioned 3 SNPs revealed a significant cumulative risk effect; the increased risk for glioma was 1.38-fold for each additional adverse genotype he or she carries (p(trend) = 8.4 × 10(-5) ). Our findings suggested that VEGFA variants may be involved in glioma risk. Larger studies with ethnically diverse populations are warranted to confirm the results reported in this investigation.


Subject(s)
Genetic Predisposition to Disease , Glioma/genetics , Polymorphism, Single Nucleotide , Vascular Endothelial Growth Factor A/genetics , Adult , Alleles , Asian People/genetics , China , Female , Gene Frequency , Genotype , Glioma/ethnology , Humans , Male , Middle Aged , Risk Factors , Young Adult
20.
Biochem Genet ; 49(3-4): 190-201, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21165767

ABSTRACT

Cytotoxic T lymphocyte-associated antigen-4 (CTLA4) A49G is a polymorphism that is extensively studied in various cancers. To investigate whether it is associated with the occurrence of glioma in Chinese patients, we performed a case-control research study with 670 patients and 680 controls. In this group, we found that the genotype at this locus is significantly associated with glioma risk (GG vs. AA: P = 0.045; GG + AG vs. AA: P = 0.013). In some subgroups, G allele carriers are significantly less represented. We also observed significant correlations between the polymorphism genotype and glioma risk in patients with WHO histologic stages. We conclude that CTLA4 A49G might be a potential clinical biomarker for distinguishing persons with a high risk for developing gliomas.


Subject(s)
Antigens, CD/genetics , Central Nervous System Neoplasms/genetics , Glioma/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Asian People , CTLA-4 Antigen , Case-Control Studies , Central Nervous System Neoplasms/ethnology , Child , Female , Genetic Association Studies , Genetic Predisposition to Disease , Glioma/ethnology , Humans , Logistic Models , Male , Risk , Risk Factors , Young Adult
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