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1.
Curr Neurovasc Res ; 19(2): 219-224, 2022.
Article in English | MEDLINE | ID: mdl-35838217

ABSTRACT

OBJECTIVE: This study aimed to investigate changes in the levels of serum lactate dehydrogenase (LDH), hypersensitive C-reactive protein (hs-CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with traumatic brain injury and the clinical significance of detecting these changes for the evaluation of injury severity and patient progress. METHODS: A retrospective study was conducted on 40 pediatric patients admitted to the Tongren Hospital of China Capital Medical University with traumatic brain injury between January 2018 and December 2019. Immunoturbidimetric assay and electrochemiluminescence were used to detect the serum levels of LDH, hs-CRP, and NT-proBNP. Correlation analysis was used to determine the degree of association between the indicators and the sensitivity and specificity of each indicator. RESULTS: The serum levels of LDH, hs-CRP, and NT-proBNP in the poor-prognosis group were higher than those in the good-prognosis group, and the differences were statistically significant (P < 0.05). CONCLUSION: The detection of serum LDH, hs-CRP, and NT-proBNP might be of great significance for the evaluation of the severity of a traumatic brain injury, disease progression, and the prognosis of pediatric patients with traumatic brain injury. The combined detection of the relevant indicators could provide more effective sensitivity and specificity and therefore offer better guidance and assistance in clinical practice.


Subject(s)
Brain Injuries, Traumatic , C-Reactive Protein , Humans , Child , C-Reactive Protein/metabolism , Retrospective Studies , Natriuretic Peptide, Brain , Peptide Fragments , Prognosis , Brain Injuries, Traumatic/diagnosis , Lactate Dehydrogenases , Biomarkers
2.
Ann Transl Med ; 10(10): 542, 2022 May.
Article in English | MEDLINE | ID: mdl-35722373

ABSTRACT

Background: The choice and efficacy of surgical or/and surgical treatments for traumatic optic neuropathy (TON) remained controversial by now. This study aims to present the outcomes of surgical and nonsurgical treatments for TON in our center. Methods: A total of 685 consecutive patients were retrospectively included in the study. And divided into surgical and non-surgical groups. All cases were treated with corticosteroids for 3 days after admission. Endoscopic optic decompression was applied to 479 patients of surgical group; The other 206 patients of nonsurgical were administered with corticosteroids alone. The visual outcomes before and after treatment were compared with Wilcoxon rank and tests. The improvement rate between two groups were compared with chi-square test. Results: The visual acuity (VA) after treatment was significantly better than that before treatment (P=0.000). Overall VA improvement rate in the surgical group was better than that in non-surgical group (42.8% vs. 35.4%) with no significant difference (P=0.072). The VA improvement rate was significant greater in the surgical group than that in the non-surgical group in the patients with NLP before treatment (P=0.028). The VA improvement rate was better in the surgical group than that in the non-surgical group (71.9% vs. 57.8%) but with no significant difference. The final overall VA was 0.1 or better in 43 cases; 104 cases were able to count fingers; hand motion (HM) became perceivable in 132 cases; light perception (LP) was achieved in 53 cases; and no light perception (NLP) remained in 353 cases. Conclusions: Endoscopic optic nerve decompression (EOND) combined with corticosteroids or corticosteroids alone could reach the improvement for patients with TON. The EOND combined with corticosteroids could achieve better VA improvement in patients with NLP.

3.
Transl Pediatr ; 10(6): 1586-1597, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34295773

ABSTRACT

BACKGROUND: This study analyzes two kinds of surgical methods for the treatment of optic pathway gliomas (OPGs) in the intraorbital segment, as well as the surgical outcomes of OPGs. METHODS: The clinical data of 86 patients with OPGs treated in our center was analyzed retrospectively, and the clinical symptoms, treatment methods, and follow-up results were recorded. RESULTS: For OPGs in the intraorbital segment, the optic nerve sheath incision was performed to remove a tumor while retaining the optic nerve sheath in Group 1 (n=36). The optic nerve sheath and the tumor were simultaneously removed without retaining the optic nerve sheath in group 2 (n=50). The effects of the design of the surgical methods on the post-surgical outcome are: One patient (1/36, 2.8%) had recurrence in Group 1 and one patient (1/50, 2.0%) had recurrence in group 2. The differences in the surgical outcomes of the two groups regarding exophthalmos, conjunctiva swelling, eye movement disorder, and ptosis were found to be statistically significant (P<0.05). Compared with group 2, the surgical outcomes in the postoperative phase of Group 1 were more satisfactory. CONCLUSIONS: The two surgical methods do not increase the recurrence rate of tumors. The resection of OPGs through an optic nerve sheath incision was found to be an ideal surgical method for reducing complications in the postoperative phase and for providing better surgical outcomes.

4.
Ann Transl Med ; 9(2): 136, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33569438

ABSTRACT

BACKGROUND: The aim of the present study was to discuss the efficacy of delayed wider endoscopic optic decompression in traumatic optic neuropathy (TON). METHODS: A total of 479 patients were treated with corticosteroids and delayed wider endoscopic optic decompression, including the injury-to-surgery interval, within 2 weeks in patients with no light perception (NLP), and within 1 month in patients with residual eyesight. Based on the traditional decompression range, the superior wall of the optic canal was further decompressed. The preoperative and postoperative visual acuities (VAs) were reviewed, and the therapeutic efficacy was analyzed. RESULTS: The final VA was 0.1 or better in 29 cases, finger count in 79 cases, hand motion in 99 cases, light perception (LP) in 25 cases, and NLP in 247 cases. A total of 136 patients (136/383, 35.5%) recovered after NLP treatment, and 78 patients (69/96, 71.9%) had improved residual eyesight. The improvement rate in patients with residual eyesight was significantly higher than that of patients with NLP (P<0.01). Moreover, the total VA after treatment was better than that before surgery (P<0.01). CONCLUSIONS: Delayed wider optic nerve decompression plus corticosteroids remains an effective and safe therapeutic strategy for patients with delayed treatment intervals of more than 1 week, especially for those with residual eyesight within 1 month.

5.
BMC Ophthalmol ; 21(1): 61, 2021 Jan 26.
Article in English | MEDLINE | ID: mdl-33499815

ABSTRACT

BACKGROUND: This study analyzed the clinical features, imaging manifestations, histopathology, immunohistochemistry, and surgical approaches of the orbital solitary fibrous tumor (OSFT), as well as the factors for postoperative recurrence of such disease. METHODS: The clinical data of 16 patients with OSFT treated in our center from 2003 to 2020 were analyzed retrospectively, and the clinical symptoms, treatment methods, and follow-up results were recorded. RESULTS: Of the 16 patients, 8 were females (50.0 %) and 8 were males (50.0 %); the average age of treatment was 37 ± 7 years and the median follow-up time was 74 (8, 228) months. Sixteen patients with OSFT underwent a total of 29 operations, of which 12 were transorbital approach operations and 17 were transfronto-orbital approach operations. Ten patients (10/16, 62.5 %) had recurrence. The recurrence rate of transorbital approach operations was 83.3 % (10/12), and the recurrence rate of transfronto-orbital approach operations was 17.6 % (3/17). No patients had treatment-related complications. CONCLUSIONS: The main pathological feature of OSFT is a benign tumor. OSFT has a tendency to grow toward the cranio-orbital junction. The postoperative recurrence rate of OSFT is relatively high, so complete tumor resection is very important for prognosis. Inappropriate surgical approaches can lead to incomplete removal of the tumor and cause recurrence. Choosing the correct operation approach according to the position of the OSFT in the orbit and complete removal of the dura mater and bone affected by the tumor is crucial for the prognosis. Nevertheless, regular long-term follow-up after complete resection is necessary.


Subject(s)
Orbital Neoplasms , Solitary Fibrous Tumors , Adult , China/epidemiology , Female , Follow-Up Studies , Humans , Male , Neoplasm Recurrence, Local/epidemiology , Orbital Neoplasms/surgery , Retrospective Studies , Solitary Fibrous Tumors/surgery , Tertiary Care Centers
6.
Front Oncol ; 11: 745479, 2021.
Article in English | MEDLINE | ID: mdl-35178343

ABSTRACT

OBJECTIVE: The present study aims to analyse the clinical presentation, treatment and prognosis of a group of patients with orbital cavernous venous malformation (OCVM) with an insidious onset. METHOD: The clinical data of 35 patients with OCVM treated at our centre between 2003 and 2020 were retrospectively analysed. The OCVMs were classified as one of six types (I-VI) according to the orbital position of the tumour. The clinical characteristics, treatment methods and follow-up results were recorded. RESULTS: A total of 35 patients with OCVM under the optic nerve sheath in the orbital apex area or the common tendon ring (Types I and II) were included in the present study. In 20 cases (57.1%), patients were misdiagnosed with optic neuritis, and in 20 cases (57.1%), the tumour was not identified based on imaging. The presentation was acute or subacute in 23 cases (65.7%). All patients underwent surgery: transnasal surgery in 22 cases (62.9%) and craniotomy in 13 cases (37.1%). A total of 9 patients (25.7%) experienced postoperative complications, and 17 patients (48.6%) experienced vision improvement. The average patient age at first diagnosis was 43.3 ± 10.3 years, and the median follow-up period was 64.5 months. Overall, 14 patients (40%) experienced postoperative complications: postoperative blindness in 6 cases, postoperative vision loss in 8 cases and orbital apex syndrome in 7 cases. CONCLUSION: Patients with Type I and Type II OCVMs are the most complex cases. They have an insidious onset and are associated with a high rate of misdiagnosis and missed diagnosis. Acute and subacute decreases in visual acuity are mainly caused by OCVM haemorrhage. The difficulty of surgical treatment and the poor prognosis of postoperative vision are characteristics of this tumour. Transnasal surgery and craniotomy can be used to remove OCVMs located in the common tendon ring or optic canal as well as those involving the intracranial area through the supraorbital fissure. Meanwhile, the orbital approach (orbitotomy) has proven to be an effective method of treating OCVMs not involving the deep orbital apex and intracranial area.

7.
Clin Chim Acta ; 512: 92-99, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33279500

ABSTRACT

BACKGROUND: The relationship between renal function and outcomes among patients with hypertrophic cardiomyopathy (HCM) remains undefined. We sought to investigate the prevalence of renal dysfunction and its prognostic value in HCM patients. METHODS: A total of 581 patients with HCM were consecutively recruited. The chronic kidney disease epidemiology equation was used to estimate the glomerular filtration rate (eGFR). Patients were divided into 2 eGFR categories: ≥60 or <60 ml/min/1.73 m2. The predictive value of renal function was assessed using Cox regression. RESULTS: The proportions of eGFR 60-90 ml/min/1.73 m2 and <60 ml/min/1.73 m2 were 41.8% and 15.3%, respectively. Estimated GFR independently predicted the risk of all-cause mortality [HR 0.98, 95% confidence interval (CI) 0.96-0.99, P < 0.001]. Compared to those with eGFR ≥ 60 ml/min/1.73 m2, patients with eGFR < 60 ml/min/1.73 m2 were independently associated with all-cause mortality (HR, 3.42 95% CI 1.86-6.28), cardiovascular mortality (HR 2.98, 95% CI 1.36-6.50) and combined adverse outcomes (HR 1.60, 95% CI 1.02-2.49). HRs for all-cause mortality with renal dysfunction were attenuated in patients with older ages (P for interaction = 0.034). CONCLUSIONS: Renal dysfunction is a common comorbidity in HCM. Renal function is an independent predictor of outcomes in patients with HCM. These findings highlight the clinical importance of renal dysfunction in HCM.


Subject(s)
Cardiomyopathy, Hypertrophic , Renal Insufficiency, Chronic , Aged , Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/diagnosis , Cohort Studies , Glomerular Filtration Rate , Humans , Middle Aged , Prognosis , Risk Factors
8.
Chem Commun (Camb) ; 54(63): 8737-8740, 2018 Aug 14.
Article in English | MEDLINE | ID: mdl-30027958

ABSTRACT

We report a novel and easy-to-fabricate polynuclear nanoparticle based on the collaborative re-assembly of nanoparticles as a robust chemogene co-delivery platform. Specifically, the polynuclear nanoparticle carrying DOX and siBcl-2 exerts remarkable co-delivery efficiency, increases tumour cell apoptosis and inhibits tumour cell proliferation in vitro and in vivo.


Subject(s)
Antineoplastic Agents/pharmacology , Doxorubicin/pharmacology , Drug Delivery Systems , Drug Design , Nanoparticles/chemistry , Polymers/chemistry , RNA, Small Interfering/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Doxorubicin/chemistry , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Particle Size , RNA, Small Interfering/chemistry , Structure-Activity Relationship , Surface Properties
9.
Biomaterials ; 113: 266-278, 2017 01.
Article in English | MEDLINE | ID: mdl-27842254

ABSTRACT

A novel biomimetic drug delivery system (BDDS) inspired by the pH-dependent ferric ion-transport and release manner of transferrin (Tf) was developed for combating multidrug-resistant breast cancer. Tf-inspired carrier was synthesized by modifying bovine serum albumin (BSA) with histamine (HA) through amide reaction to provide superior specific coordination sites for ferric ion-drug complexes, and self-assembled into nanoparticles (NPs) induced by coordination bond. Tf-inspired NPs were prepared via environment-friendly method, and well redispersed in saline after lyophilization. When internalized into tumor cells by SPARC (secreted protein acidic and rich in cysteine) mediated endocytosis, Tf-inspired NPs bypassed and decreased the P-glycoprotein-mediated drug efflux and led to more effective treatment of multidrug-resistant breast cancer compared with free drugs both in vitro and in vivo due to the enhanced cellular uptake and rapid pH-responsive drug release. Moreover, Tf-inspired NPs exhibited good biocompatibility and low systemic toxicity. Thus, our results demonstrate that Tf-inspired NPs based on coordination bond represent as a smart drug delivery strategy to combat multidrug-resistant cancer and have great potential for clinical applications in cancer therapy.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Breast Neoplasms/drug therapy , Delayed-Action Preparations/chemistry , Doxorubicin/administration & dosage , Nanoparticles/chemistry , Transferrin/analogs & derivatives , Animals , Antibiotics, Antineoplastic/pharmacokinetics , Antibiotics, Antineoplastic/therapeutic use , Breast/drug effects , Breast/pathology , Breast Neoplasms/pathology , Cattle , Cell Line, Tumor , Doxorubicin/pharmacokinetics , Doxorubicin/therapeutic use , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Female , Histamine/analogs & derivatives , Humans , Hydrogen-Ion Concentration , Mice, Inbred BALB C , Mice, Nude , Serum Albumin, Bovine/chemistry
10.
Int J Pharm ; 513(1-2): 612-627, 2016 Nov 20.
Article in English | MEDLINE | ID: mdl-27682215

ABSTRACT

This report demonstrated a one-step assembly for co-delivering chemotherapeutics and therapeutic nucleic acids, constructed by integrating drug molecules into a nucleic acid condensing polymeric prodrug through degradable linkages. Demethylcantharate was selected as the model drug and pre-modified by esterifying its two carboxylic groups with 2-hydroxyethyl acrylate. The synthesized demethylcantharate diacrylate was then used to polymerize with linear polyethyleneimine (PEI 423) through a one-step Michael-addition reaction. The obtained cationic polymeric demethylcantharate prodrug was used to pack Akt1 shRNA into complexes through a one-step assembly. The formed complexes could release the parent drug demethylcantharate and Akt1 shRNA through the hydrolysis of ester bonds. Cellular assays involving cell uptake, cytotoxicity, and cell migration indicated that demethylcantharate and Akt1 shRNA co-delivered in the present form significantly and synergistically suppress the growth and metastasis of three human cancer cells. This work suggests that incorporating drug molecules into a nucleic acid-packing cationic polymer as a polymeric prodrug in a degradable form is a highly convenient and efficient way to co-deliver drugs and nucleic acids for cancer therapy.


Subject(s)
Acrylates/chemistry , Antineoplastic Agents/chemistry , Cantharidin/analogs & derivatives , Polymers/chemistry , Prodrugs/chemistry , Proto-Oncogene Proteins c-akt/genetics , Acrylates/administration & dosage , Acrylates/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacology , Cantharidin/administration & dosage , Cantharidin/chemistry , Cantharidin/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , DNA/administration & dosage , DNA/chemistry , DNA/pharmacology , Drug Liberation , Green Fluorescent Proteins/genetics , Humans , Hydrolysis , Polymerization , Polymers/administration & dosage , Polymers/pharmacology , Prodrugs/administration & dosage , Prodrugs/pharmacology , RNA, Small Interfering/chemistry
11.
Int J Pharm ; 506(1-2): 207-13, 2016 Jun 15.
Article in English | MEDLINE | ID: mdl-27113867

ABSTRACT

Based on development of nano-delivery system, co-delivery of chemotherapeutic drug and small interfering RNA (siRNA) has exerted a promising advantage in cancer therapy. In this work, the superiority of synergistic therapy and safety of the hierarchical targeted co-delivery system loaded with siRNA and lonidamine (LND) were evaluated. The in vivo tumor accumulation ability and cancer growth inhibition effect of the polymer-blend nanocarriers were evaluated by a H22 subcutaneous sarcoma model. Moreover, hematoxylin and eosin (H&E) staining and transferase-mediated dUTP nick end-labeling (TUNEL) staining of tumor sections from each group were compared to assess the therapeutic efficacy. The dual-loaded nanocarriers had better tumor accumulation ability, remarkably inhibited growth of solid tumor in a synergistic manner, even significantly decreased hepatotoxicity of LND, and had good in vivo biocompatibility whereas LND alone showed serious hepatotoxicity. We believed that the dual-loaded hierarchical targeted delivery system with high effectiveness and biocompatibility would provide a promising approach for cancer combination therapy.


Subject(s)
Antineoplastic Agents/administration & dosage , Indazoles/administration & dosage , RNA, Small Interfering/administration & dosage , Sarcoma/drug therapy , Animals , Antineoplastic Agents/pharmacology , Drug Carriers/chemistry , Drug Delivery Systems , In Situ Nick-End Labeling , Indazoles/pharmacology , Male , Mice , Mice, Inbred ICR , Nanoparticles , Polymers/chemistry , Sarcoma/genetics , Xenograft Model Antitumor Assays
12.
Int J Pharm ; 506(1-2): 79-86, 2016 Jun 15.
Article in English | MEDLINE | ID: mdl-27102990

ABSTRACT

Polyamine content, which is associated with tumor growth, can be regulated by ornithine decarboxylase (ODC) and S-adenosyl methionine decarboxylase (SAMDC), two key enzymes in polyamine biosynthesis. Here we aim to develop a pH-responsive cationic poly(agmatine) based on a polyamine analogue-agmatine that can dually function as a gene delivery vector as well as an anticancer agent by inhibiting ODC after intracellular degradation. The core-shell nanoparticles, formed by poly(agmatine)/SAMDC siRNA complex as a core, were coated with bovine serum albumin for better in vivo circulation stability and tumor targeting. When the nanoparticles were taken up by tumor cells via endocytosis and degraded in endosome, the released agmatine and SAMDC siRNA can synergistically inhibit polyamines biosynthesis, inducing inhibition of tumor proliferation. Our study offered a potential way in tumor therapy based on polyamine metabolism.


Subject(s)
Antineoplastic Agents/administration & dosage , Cell Proliferation/drug effects , Neoplasms/drug therapy , Polyamines/metabolism , Adenosylmethionine Decarboxylase/metabolism , Cell Line, Tumor , Endocytosis/drug effects , Endosomes/metabolism , Gene Transfer Techniques , Hep G2 Cells , Humans , MCF-7 Cells , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Neoplasms/metabolism , Ornithine Decarboxylase/metabolism , RNA, Small Interfering/metabolism , Serum Albumin, Bovine/chemistry
13.
Biomaterials ; 73: 149-59, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26409000

ABSTRACT

Combination therapy is usually considered as a promising strategy owing to its advantages such as reduced doses, minimized side effects and improved therapeutic efficiency in a variety of diseases including diabetes. Here we synthesized a new highly intracellular stimuli-sensitive chitosan-graft-metformin (CS-MET) prodrug by imine reaction between oxidative chitosan and metformin for type 2 diabetes (T2D) therapy. Hypothetically, CS-MET functions dually as an anti-diabetes prodrug as well as a gene delivery vector without superfluous materials. CS-MET formed nanocomplexes with therapeutic gene through electrostatic interactions and entered cells by Organic Cation Transporter (OCT)-independent endocytosis. The incorporation of metformin into chitosan has been found to increase endosomal escape via the proton sponge effect. When vector carrying a short-hairpin RNA (shRNA) silencing sterol regulatory element-binding protein (SREBP), a major transcription factor involved in de novo lipogenisis, it reduced the SREBP mRNA and proteins efficiently. Furthermore, by intraperitoneal injection, CS-MET/shSREBP nanocomplexes effectively knocked down SREBP in livers of western-type diet (WD)-induced obese C57BL/6J mice, markedly reversed insulin resistance and alleviated the fatty liver phenotype without obvious toxic effects. Thus we were able to show that the intracellular stimuli-sensitive CS-MET prodrug renders a potential platform to increase the anti-diabetes activity with synergistic enhancement of gene therapy.


Subject(s)
Diabetes Mellitus, Type 2/therapy , Nanostructures/chemistry , Polymers/chemistry , Prodrugs/chemistry , Animals , Biocompatible Materials/chemistry , Cell Line, Tumor , Chitosan/administration & dosage , Endocytosis , Fatty Liver/metabolism , Genetic Therapy/methods , Genetic Vectors , Glucose Tolerance Test , Hep G2 Cells , Homeostasis , Humans , Imines/chemistry , Lipids/chemistry , Metformin/administration & dosage , Metformin/chemistry , Mice , Mice, Inbred C57BL , Mice, Obese , Microscopy, Confocal , Oxygen/chemistry , Phenotype , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Static Electricity , Sterol Regulatory Element Binding Protein 1/chemistry
14.
Chin Med J (Engl) ; 128(17): 2307-11, 2015 Sep 05.
Article in English | MEDLINE | ID: mdl-26315077

ABSTRACT

BACKGROUND: Tuberculum sellae meningiomas (TSMs) present a special symptom because of the adherence and compression to the optic nerve, optic artery, and the chiasm. A significant number of patients with TSMs appear visual deficits. This study aimed to investigate the surgical indications of exploring the optic canal and visual prognostic factors in the neurosurgical treatment of TSMs. METHODS: Totally 21 patients with TSM, who were operated from September 2007 to August 2011 in the Department of Neurosurgery, Tongren Hospital were enrolled in this study. Results of orbital computed tomography (CT) and magnetic resonance imaging (MRI), visual acuity, Goldmann visual field test, orbital color Doppler flow imaging (CDI) test in these patients were retrospectively analyzed. RESULTS: Visual deficit and optic canal involvement (OCI) were detected in all the 21 patients. Fourteen patients had bone proliferation within the area of the optic canal. After the operation, visual outcomes were improved in 13 patients, unchanged in 7 patients, and deteriorated in 1 patient. All the 21 patients performed orbital CDI test preoperatively, the results showed that if the peak systolic velocity (PSV) of central retinal artery (CRA) value was ≤ 8 cm/s, the visual outcome would be better. CONCLUSIONS: The surgical indications of exploring optic canal in TSM cases included: (1) The neuroimaging evidences of OCI (CT and/or MRI); (2) PSV of CRA in orbital CDI test was ≤ 8 cm/s; (3) visual acuity was below 0.1; (4) visual field deficit. The PSV of CRA in CDI test could be a prognostic factor for visual outcomes of TSMs.


Subject(s)
Meningeal Neoplasms/surgery , Meningioma/surgery , Adult , Aged , Female , Humans , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Middle Aged , Neurosurgical Procedures/methods , Retrospective Studies , Sella Turcica/pathology , Sella Turcica/surgery , Skull Base Neoplasms/pathology , Skull Base Neoplasms/surgery , Visual Acuity
15.
Biomaterials ; 61: 178-89, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26004233

ABSTRACT

The mitochondria-mediated apoptosis pathway is an effective option for cancer therapy due to the presence of cell-suicide weapons in mitochondria. However, anti-apoptotic proteins that are over-expressed in the mitochondria of many malignant tumors, such as Bcl-2 protein, could allow the cancer cells to evade apoptosis, greatly reducing the efficacy of this type of chemotherapy. Here, we constructed a hierarchical targeted delivery system that can deliver siRNA and chemotherapeutic agents sequentially to tumor cells and mitochondria. In detail, the copolymer TPP-CP-LND (TCPL) was synthesized by the mitochondria-targeting ligand triphenylphosphine (TPP) and therapeutic drug lonidamine (LND) conjugated to the polyethyleneimine in chitosan-graft-PEI (CP), and then complexed with siRNA. Followed, the complexes were coated with poly(acrylic acid)-polyethylene glycol-folic acid (PPF) copolymer to form a hierarchical targeted co-delivery system (TCPL/siRNA/PPF NPs). The TCPL/siRNA/PPF NPs had a neutral surface charge, were stable in plasma and exhibited pH-responsive shell separation. Remarkably, the TCPL/siRNA/PPF NPs simultaneously released siBcl-2 into the cytoplasm and delivered LND to mitochondria in the same cancer cell after FA-directed internalization, and even synergistically activated mitochondria apoptosis pathway. This work demonstrated the potential of RNA-interference and mitochondria-targeted chemotherapeutics to collaboratively stimulate the mitochondria apoptosis pathway for cancer therapy.


Subject(s)
Apoptosis Regulatory Proteins/metabolism , Apoptosis/physiology , Indazoles/administration & dosage , Mitochondria/physiology , Nanocapsules/chemistry , RNA, Small Interfering/administration & dosage , Antineoplastic Agents/administration & dosage , Apoptosis/drug effects , Diffusion , HeLa Cells , Humans , Indazoles/chemistry , Mitochondria/drug effects , Mitochondrial Proteins/metabolism , Nanocapsules/ultrastructure , RNA, Small Interfering/genetics , Signal Transduction/drug effects , Signal Transduction/physiology , Treatment Outcome
16.
Oncotarget ; 5(14): 5591-601, 2014 Jul 30.
Article in English | MEDLINE | ID: mdl-25015320

ABSTRACT

Nasopharyngeal carcinoma (NPC) is one of the severe head and neck carcinomas, which is rare in west countries but has high incidence in Southern Asia especially South China. Although NPC is relatively sensitive to radiotherapy, the prognosis of patients is poor due to the advanced stage at the time of diagnosis. Therefore, it is important to understand the mechanisms involved in tumorigenesis and develop early diagnostic techniques. S-phase kinase associated protein 2 (Skp2) is overexpressed in several human cancers and associates with poor prognosis. However, its function in NPC has not been fully addressed. In this study we found Skp2 was highly expressed in NPC specimen and correlated with poor prognosis. We generated Skp2 knockdown cells to further delineate its role in NPC development. Knockdown of Skp2 partially reduced cell proliferation, promoted cellular senescence, and decreased the population of stem cell like aldehyde dehydrogenase1 positive cells as well as their self-renewal ability. Our study not only interprets the predictive role of Skp2 in the poor prognosis of NPC patients, but also reveals that Skp2 regulates the NPC cancer stem cell maintenance, which shed lights on the target therapy and early diagnosis of NPC in clinical application.


Subject(s)
Nasopharyngeal Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , S-Phase Kinase-Associated Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Adult , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma , Cell Proliferation/physiology , Female , Humans , Male , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/enzymology , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/pathology , Neoplasm Metastasis , Neoplasm Recurrence, Local/enzymology , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplastic Stem Cells/enzymology , Neoplastic Stem Cells/pathology , Prognosis , S-Phase Kinase-Associated Proteins/genetics , Ubiquitin-Protein Ligases/genetics
17.
Nat Commun ; 5: 3661, 2014 Apr 17.
Article in English | MEDLINE | ID: mdl-24739462

ABSTRACT

Lack of cellular differentiation is a key feature of nasopharyngeal carcinoma (NPC), but it also presents as a unique opportunity for intervention by differentiation therapy. Here using RNA-seq profiling analysis and functional assays, we demonstrate that reduced IKKα expression is responsible for the undifferentiated phenotype of NPC. Conversely, overexpression of IKKα induces differentiation and reduces tumorigenicity of NPC cells without activating NF-κB signalling. Importantly, we describe a mechanism whereby EZH2 directs IKKα transcriptional repression via H3K27 histone methylation on the IKKα promoter. The differentiation agent, retinoic acid, increases IKKα expression by suppressing EZH2-mediated H3K27 histone methylation, resulting in enhanced differentiation of NPC cells. In agreement, an inverse correlation between IKKα (low) and EZH2 (high) expression is associated with a lack of differentiation in NPC patient samples. Collectively, these findings demonstrate a role for IKKα in NPC differentiation and reveal an epigenetic mechanism for IKKα regulation, unveiling a new avenue for differentiation therapy.


Subject(s)
I-kappa B Kinase/metabolism , Nasopharyngeal Neoplasms/metabolism , Polycomb Repressive Complex 2/metabolism , Blotting, Western , Carcinoma , Cell Cycle/genetics , Cell Cycle/physiology , Cell Differentiation/genetics , Cell Differentiation/physiology , Cell Line, Tumor , Chromatin Immunoprecipitation , Enhancer of Zeste Homolog 2 Protein , Epigenesis, Genetic/genetics , Fluorescent Antibody Technique , Gene Expression Regulation, Neoplastic , Humans , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/genetics , Polycomb Repressive Complex 2/genetics , RNA, Small Interfering , Reverse Transcriptase Polymerase Chain Reaction
18.
Zhongguo Gu Shang ; 25(10): 870-1, 2012 Oct.
Article in Chinese | MEDLINE | ID: mdl-23342808

ABSTRACT

OBJECTIVE: To observe therapeutic effects of preventing degenerative osteoarthritis by injecting bone cement into tibial condyle. METHODS: From January 2006 to Junary 2009, 24 patients with degenerative osteoarthritis were treated by injecting bone cement into tibial condyle, including 10 males and 14 females, ranging in age from 46 to 65 years, with an average of 50 years. The mean course of duation was 1 year. HSS scoring system was used to evaluate therapeutic effects preoperatively and one year after follow-up. RESULTS: All patients were followed up over 2 years. HSS score after two years follow-up was 66.65 +/- 6.30, which was higher than that of preoperative 35.70 +/- 4.80. There was no significant difference between preoperation and one year after follow-up in anatomy angle of tibia. CONCLUSION: Bone cement injection into tibial condyle can prevent degenerative osteoarthritis and varus knee.


Subject(s)
Bone Cements/therapeutic use , Osteoarthritis, Knee/prevention & control , Aged , Female , Humans , Injections , Male , Middle Aged , Tibia
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(10): 2812-5, 2010 Oct.
Article in Chinese | MEDLINE | ID: mdl-21137427

ABSTRACT

Optical emission spectroscopy (OES) was adopted for the first time by our group for in situ diagnosis of the conversion of CH4-H2 under glow discharge plasma at atmospheric pressure with rotary electrodes. The emission of excited species such as excited radicals and atoms (C, CH, C2, H and H2) was detected in the spectra range of 300-700 nm. The spectrum of hydrogen atom was used to figure out the plasma excitation temperature by a Boltzmann plot scheme. It was evaluated that the excitation temperature of hydrogen plasmas under varied discharge conditions is in the range of 6300-6600 K. The electron density was calculated based on spectral profile of H lines and its order is about 10(20) m(-3).

20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(5): 1167-70, 2010 May.
Article in Chinese | MEDLINE | ID: mdl-20672593

ABSTRACT

An arc plasma discharge with a long length of 20 cm was generated in a quartz capillary between two hollow needle electrodes in argon at atmospheric pressure with use of the sinusoidal power supply operating at 45 kHz, which was characterized by a very high electron density. The spectroscopic method of optical emission was employed to diagnose the characteristic parameters of the arc plasma discharge in the quartz capillary. The gas temperature was determined by simulating the OH A-X(0, 0) vibrational band around 300 nm and comparison with measured spectrum by means of optical emission spectroscopy. Furthermore, the electron density was measured by means of Stark broadening of the profile of Hbeta at 486.1 nm. The electron temperature was determined using a Boltzmann plot method. The experiment results show that in the argon arc plasma discharge generated in the quartz capillary at atmospheric pressure, the gas temperature of plasma is about (1 100 +/- 50)K, the electron density at the gas temperature of 1 100 K is approximately 10(14) cm(-3), and the corresponding electron temperature is (14 515 +/- 500)K. This work has accumulated some significant experimental parameters for the treatment of inner surface of large length-to-radius-ratio insulated dielectric tube using plasma, and the results are of great importance to the applications of this type of atmospheric-pressure plasma discharge.

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