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1.
Int J Cancer ; 152(5): 962-976, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36214789

RESUMO

Cervical cancer remains a major threat to women's health, especially in countries with limited medical resources, and new drugs are needed to improve patient survival and minimize adverse effects. Here, we examine the effects of a triphenylphosphonium (TPP)-conjugated pyrrole-imidazole polyamide (CCC-h1005) targeting the common homoplasmic mitochondrial DNA (mtDNA) cancer risk variant (ATP6 8860A>G) on the survival of cervical cancer cell lines, cisplatin-resistant HeLa cells and patient-derived cervical clear cell carcinoma cells as models of cervical cancer treatment. We found that CCC-h1005 induced death in these cells and suppressed the growth of xenografted HeLa tumors with no severe adverse effects. These results suggest that PIP-TPP designed to target mtDNA cancer risk variants can be used to treat many cervical cancers harboring high copies of the target variant, providing a foundation for clinical trials of this class of molecules for treating cervical cancer and other types of cancers.


Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Nylons/farmacologia , DNA Mitocondrial/genética , Células HeLa , Pirróis/farmacologia , Imidazóis/farmacologia
2.
Biomater Adv ; 134: 112584, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35525738

RESUMO

It's an exigent need for the improvement of novel antibacterial wound dressings with the increasing threats of drug resistance caused by excessive use of the antibiotics. In this work, an injectable, adhesive, hemostatic, biocompatible and bactericidal hydrogel wound dressing was fabricated. An injectable hydrogel can fill the irregular wound due to the characteristic of reversible sol-gel transition, whereas conventional dressings don't possess this ability. Oxidized alginate (ADA) and catechol-modified gelatin (Gel-Cat) were selected as the polymer backbones and they can crosslink in situ through double dynamic bonds, which were Schiff base and catechol-Fe coordinate bond; polydopamine decorated silver nanoparticles (PDA@Ag NPs) were also introduced into the hydrogel network. The double dynamic bonds endowed the hydrogel with injectable ability, shorter gelation time and enhanced mechanical property. And the aldehyde and catechol groups on the chains of ADA and Gel-Cat gave the hydrogel excellent adhesiveness. In addition, the PDA@Ag NPs in this system play two roles: one is bactericidal agent which can release from the hydrogel to kill the bacteria; the other is photothermal agent to convert 808 nm near-infrared light into heat to realize sterilization. In vitro study, the hydrogel displayed bactericidal ability against S. aureus and E. coli whether in photothermal antimicrobial test or agar diffusion test. In vivo test also testified that the hydrogel had a prominent therapeutic effect on infected wound through reducing inflammatory response and accelerating angiogenesis. Thus, we anticipate that our double dynamic bonds crosslinked hydrogel with PDA@Ag NPs as the antimicrobial agent can be a novel therapeutic way for infected wounds.


Assuntos
Nanopartículas Metálicas , Infecção dos Ferimentos , Adesivos/farmacologia , Antibacterianos/farmacologia , Bandagens , Catecóis/farmacologia , Escherichia coli , Gelatina/farmacologia , Humanos , Hidrogéis/química , Nanopartículas Metálicas/uso terapêutico , Prata/farmacologia , Staphylococcus aureus , Infecção dos Ferimentos/tratamento farmacológico
3.
J Oncol ; 2021: 1331031, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868310

RESUMO

BACKGROUND: High-grade serous ovarian cancer (HGSOC) carries the highest mortality in the gynecological cancers; however, therapeutic outcomes have not significantly improved in recent decades. Macrophages play an essential role in the occurrence and development of ovarian cancer, so the mechanisms of macrophage infiltration should be elucidated. METHOD: We downloaded transcriptome data of ovarian cancers from the Gene Expression Omnibus and The Cancer Genome Atlas. After rigorous screening, 1566 HGSOC were used for data analysis. CIBERSORT was used to estimate the level of macrophage infiltration and WGCNA was used to identify macrophage-related modules. We constructed a macrophage-related prognostic model using machine learning LASSO algorithm and verified it using multiple HGSOC cohorts. RESULTS: In the GPL570-OV cohort, high infiltration level of M1 macrophages was associated with a good outcome, while high infiltration level of M2 macrophages was associated with poor outcomes. We used WGCNA to select genes correlated with macrophage infiltration. These genes were used to construct protein-protein interaction maps of macrophage infiltration. IFL44L, RSAD2, IFIT3, MX1, IFIH1, IFI44, and ISG15 were the hub genes in the network. We then constructed a macrophage-related prognostic model composed of CD38, ACE2, BATF2, HLA-DOB, and WARS. The model had the ability to predict the overall survival rate of HGSOC patients in GPL570-OV, GPL6480-OV, TCGA-OV, GSE50088, and GSE26712. In exploring the immune microenvironment, we found that CD4 memory T cells and activated mast cells showed that the degree of infiltration was higher in the high-risk group, while M1 macrophages were the opposite, and HLA molecules were overexpressed in the high-risk group. CONCLUSION: We constructed a macrophage infiltration-related protein interaction network that provides a basis for studying macrophages in HGSOC. Our macrophage-related prognostic model is robust and widely applicable. It predicts overall survival in HGSOC patients and may improve HGSOC treatment.

4.
Front Oncol ; 11: 650678, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868901

RESUMO

BACKGROUND: Bladder cancer lacks useful and robust prognostic markers to stratify patients at risk. Our study is to identify a robust prognostic marker for bladder cancer. METHODS: The transcriptome and clinical data of bladder cancer were downloaded from multiple databases. We searched for genes with robust prognosis by Kaplan-Meier analysis of the whole genome. CIBERSORT and TIMER algorithm was used to calculate the degree of immune cell infiltration. RESULTS: We identified OLFML2B as a robust prognostic marker for bladder cancer in five cohorts. Kaplan-Meier analysis showed that patients with a high level of OLFML2B expression had a poor prognosis. The expression of OLFML2B increased with the increase of stage and grade. We found that patients with high expression of OLFML2B still had a poor prognosis in two small bladder cancer cohorts. OLFML2B also has the prognostic ability in ten other tumors, and the prognosis is poor in high expression. The correlation analysis between OLFML2B and immune cells showed that it was positively correlated with the degree of macrophage infiltration and highly co-expressed with tumor-associated macrophage markers. Finally, the Wound-healing assay and Colony formation assay results showed that the migration and proliferation ability of bladder cancer cell lines decreased after the knockdown of OLFML2B. CONCLUSIONS: In summary, OLFML2B is a robust risk prognostic marker, and it can help patients with bladder cancer improve individualized treatment.

5.
Mater Sci Eng C Mater Biol Appl ; 130: 112451, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34702530

RESUMO

Long carbon fiber reinforced polyether ether ketone (LCFRPEEK) is fabricated using a three-dimensional (3D) needle-punched method in our previous work, which is considered as a potential orthopedic implant due to its high mechanical strength and isotropic properties, as well as having an elastic modulus similar to human cortical bone. However, the LCFRPEEK has inferior integration with bone tissue, limiting its clinical application. Thus, a facile surface modification method, using gelatin methacrylate/polyacrylamide composite hydrogel coating (GelMA/PAAM) loading with dexamethasone (Dex) on our newly-developed LCFRPEEK composite via concentrated sulfuric acid sulfonating and ultraviolet (UV) irradiation grafting methods, has been developed to tackle the problem. The results demonstrate that the GelMA/PAAM/Dex coating modified sulfonated LCFRPEEK (SCP/GP/Dex) has a hydrophilicity surface, a long-term Dex release capability and forms more bone-like apatite nodules in SBF. The SCP/GP/Dex also displays enhanced cytocompatibility and osteogenic differentiation in terms of rat bone marrow mesenchymal stem cells (rBMSCs) responses in vitro assay. The in vivo rat cranial defect assay confirms that SCP/GP/Dex boosts bone regeneration/osseointegration, which significantly improves osteogenic fixation between the implant and bone tissue. Therefore, the newly-developed LCFRPEEK modified via GelMA/PAAM/Dex bioactive coating exhibits improved biocompatibility and osteogenic integration capability, which has the basis for an orthopedic implant for clinical application.


Assuntos
Hidrogéis , Osteogênese , Animais , Fibra de Carbono , Proliferação de Células , Éteres , Cetonas/farmacologia , Ratos
6.
J Mater Chem B ; 9(36): 7492-7505, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551047

RESUMO

A resveratrol-loaded bi-layered scaffold (RBS) that consists of a resveratrol-loaded poly(lactic-co-glycolic acid) (Res-PLGA) electrospinning nanofiber mat (upper layer) and an alginate di-aldehyde (ADA)-gelatin (GEL) crosslinking hydrogel (ADA-GEL) (lower layer) was fabricated as a wound dressing material. It was made through mimicking the epidermis and dermis of the skin. The RBS exhibited good hemostatic ability and proper swelling ability. Furthermore, HaCaT cells and human embryonic skin fibroblasts (ESFs) were also cultured in the nanofiber layer and hydrogel layer of RBS, and the results indicated that both HaCaT and ESFs could grow well in the materials. The in vivo experiment using a Sprague-Dawley (SD) rat skin wound as a model showed that the RBS could accelerate the wound healing rate compared with the Res-PLGA group and ADA4-GEL6 group. These results indicated that this resveratrol-loaded bi-layered scaffold can be a potential candidate in promoting wound healing.


Assuntos
Alginatos/química , Gelatina/química , Hidrogéis/química , Nanofibras/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Hidrogéis/farmacologia , Ratos , Ratos Sprague-Dawley , Resveratrol/química , Resveratrol/metabolismo , Resveratrol/farmacologia , Reologia , Pele/lesões , Pele/patologia , Cicatrização/efeitos dos fármacos
7.
Front Immunol ; 12: 657951, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531849

RESUMO

Kidney renal papillary cell carcinoma (KIRP), the second most common subtype of renal cell carcinoma, still lacks effective treatment regimens for individualized immunotherapy because of the heterogeneity of its elusive immune microenvironment. Therefore, we aimed to comprehensively evaluate the immune microenvironment of KIRP by using the computational biology strategy to analyze the expression profile data of 289 KIRP patients obtained from The Cancer Genome Atlas database. Based on multidimensional, multi-omics bioinformatics analysis, we found that the tumor of patients with KIRP exhibited "hot" tumor characteristics but the CD8+ T cells in the tumor tissues did not limit tumor progression. Thus, patients with KIRP may realize higher clinical benefits by receiving treatment that can reverse CD8+ T-cell exhaustion. Among them, C1 and C3 immune subtypes could realize the best efficacy of reversing CD8+ T-cell exhaustion. Moreover, CCL5 and FASLG expression may be related to the formation of the immunosuppressive microenvironment in the tumors of patients with KIRP. In conclusion, the immune microenvironment landscape presented in this study provides a novel insight for further experimental and clinical exploration of tailored immunotherapy for patients with KIRP.


Assuntos
Carcinoma de Células Renais/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Microambiente Tumoral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/terapia , Feminino , Ontologia Genética , Redes Reguladoras de Genes/genética , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
8.
World J Clin Cases ; 9(6): 1439-1445, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33644213

RESUMO

BACKGROUND: Postoperative discal pseudocyst (PDP) is a rare condition that presents after surgery for lumbar disc herniation. Due to the lack of information, the diagnosis and treatment of PDP remain controversial. Herein, we report a PDP case that occurred following percutaneous endoscopic lumbar discectomy and received conservative treatment. Additionally, we review all the published literature regarding PDP and propose our hypothesis regarding PDP pathology. CASE SUMMARY: A 23-year-old man presented with a relapse of low back pain and numbness in his left lower extremity after undergoing percutaneous endoscopic lumbar discectomy for lumbar disc herniation. Repeat magnetic resonance imaging demonstrated a cystic lesion at the surgical site with communication with the inner disc. The patient was diagnosed as having PDP. The patient received conservative treatment, which resulted in rapid improvement and spontaneous regression of the lesion, and had a favorable outcome in follow-up. CONCLUSION: PDP and discal cyst (DC) exhibit similarities in both histological and epidemiological characteristics, which indicates the same pathological origin of PDP and DC. The iatrogenic annular injury during discectomy might accelerate the pathological progression of DC. For patients with mild to moderate symptoms, conservative treatment can lead to great improvement, even inducing spontaneous regression. However, surgical cystectomy is necessary in patients with neurological deficits and where conservative treatment is ineffective.

9.
Medicine (Baltimore) ; 99(50): e23704, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327361

RESUMO

RATIONALE: Floating ankle is a rare traumatic condition characterized by a combination of tibial and ipsilateral foot fractures, with the ankle remaining intact. It is usually caused by high-energy trauma and also presents with serious soft tissue damage. Its treatment is mainly restricted to external fixation, which results in poor outcomes. We present a patient with a floating ankle who underwent staged treatment and achieved full internal fixation, subsequently returning to normal activity. PATIENT CONCERNS: A 26 year- old man had an accident with an reel machine and sustained an open fracture on his right lower extremity. DIAGNOSES: Digital radiograph demonstrated a distal tibial fracture, fibular fracture, and multiple metatarsal fractures, which fulfilled the criteria for a floating ankle. INTERVENTIONS: Initial ankle-spanning external fixation was performed. After 21 days, the patient underwent open reduction and internal fixation on his first and fifth metatarsals, and K-wire fixation on his fourth metatarsal. The external fixator was replaced by plaster fixation. Seven days later, the patient underwent internal fixation of his leg, open reduction and internal fixation with plating was applied of the fibular fracture, and minimally invasive plate osteosynthesis of the tibial fracture. OUTCOMES: At 1-year follow-up, bone union was identified by digital radiograph; after 2 years, his ankle function had fully recovered, and he resumed his normal activities. LESSONS: In the staged treatment protocol of the floating ankle, temporary external fixation provided traction and immobilization of the skeletal and soft tissues. Secondary internal fixation maintained the reduction and alignment and allowed early exercise, which is critical to the prognosis of a floating ankle.


Assuntos
Traumatismos do Tornozelo/cirurgia , Ossos do Pé/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas Expostas/cirurgia , Fraturas da Tíbia/cirurgia , Adulto , Placas Ósseas , Fios Ortopédicos , Ossos do Pé/lesões , Humanos , Masculino , Amplitude de Movimento Articular
10.
Biomed Res Int ; 2020: 2829647, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685461

RESUMO

BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) has been reported as a rare disease with low malignant potential. The aim of this study was to summarize experiences of the diagnosis and treatment for the patients reported in the Chinese population. METHOD: 2450 SPTP cases reported in English and Chinese literature before Jan 2020 were for our review and analysis retrospectively. RESULT: There are 389 male cases and 2061 female cases, and the ratio of male/female was 1 : 5.3. The average age was 29.3 years. The main clinical symptoms were upper abdominal pain and bloating discomfort in 51.6% of the cases and epigastric mass. 38.6% of the tumor was located at the head of the pancreas and 55.4% at the body and tail of the pancreas. The most frequent operative styles were tumor enucleation (38.4%). Pathology showed that the average diameter of the tumor was 8.2 cm and 12.3% of SPTP was malignant. 98.3% of cases had favorable survival. CONCLUSIONS: SPTP is a rare indolent tumor occurring mainly in young women, and the main clinical performances are abdominal mass and abdominal pain; most tumors are distributed at the head and the tail of the pancreas; the prognosis after complete resection is excellent.


Assuntos
Povo Asiático , Carcinoma Papilar/patologia , Neoplasias Pancreáticas/patologia , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Seguimentos , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/etiologia
11.
ACS Biomater Sci Eng ; 6(5): 2970-2984, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33463266

RESUMO

Calcium phosphate cements (CPCs) have been widely used for the study of bone regeneration because of their excellent physical and chemical properties, but poor biocompatibility and lack of osteoinductivity limit potential clinical applications. To overcome these limitations, and based on our previous research, CPC scaffolds were prepared with CPC as the principal material and polyethylene glycol (PEG) as a porogen to introduce interconnected macropores. Using a bespoke electrospinning auxiliary receiver, silk fibroin (SF)/poly(lactide-co-glycolide) (PLGA) coaxial nanofibers containing dexamethasone (DXM) and recombinant human bone morphogenetic protein-2 (rhBMP2) were fabricated which were coated on the surface of the CPC. By comparing the surface morphology by SEM, hydrophilicity, results of FTIR spectroscopy, and mechanical properties of the composite materials fabricated using different electrospinning times (20, 40, 60 min), the CPC surface constructed by electrospinning for 40 min was found to exhibit the most appropriate physical and chemical properties. Therefore, composite materials were built for further study by electrospinning for 40 min. The osteogenic capacity of the SF/PLGA/CPC, SF-DXM/PLGA/CPC, and SF-DXM/PLGA-rhBMP2/CPC scaffolds was evaluated by in vitro cell culture with rat bone marrow mesenchymal stem cells (BMSCs) and using a rat cranial defect repair model. ALP activity, calcium deposition levels, upregulation of osteogenic genes, and bone regeneration in skull defects in rats with SF-DXM/PLGA-rhBMP2/CPC implants were significantly higher than in rats implanted with the other scaffolds. These results suggest that drug-loaded coaxial nanofiber coatings prepared on a CPC surface can continuously and effectively release bioactive drugs and further stimulate osteogenesis. Therefore, the SF-DXM/PLGA-rhBMP2/CPC scaffolds prepared in this study demonstrated the most significant potential for the treatment of bone defects.


Assuntos
Fibroínas , Nanofibras , Animais , Regeneração Óssea , Fosfatos de Cálcio , Proliferação de Células , Ratos , Alicerces Teciduais
12.
Am J Cancer Res ; 8(8): 1483-1498, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210918

RESUMO

Cervical cancer is one of the most common cancers in females, accounting for a majority of cancer-related deaths in worldwide. Long non-coding RNAs (lncRNAs) have been identified as critical regulators in many tumor-related biological processes. Thus, investigation into the function and mechanism of lncRNAs in the development of cervical cancer is very necessary. In this study, we found that the expression of TOB1-AS1 was significantly decreased in cervical cancer tissues compared with the adjacent normal tissues. The methylation status of TOB1-AS1-related CpG island was analyzed using methylation specific PCR and bisulfite sequencing analysis, revealing that the aberrant hypermethylation of TOB1-AS1-related CpG island was frequently observed in primary tumors and cervical cancer cells. The expression of TOB1-AS1 in cervical cancer cells could be reversed by demethylation agent treatment. Functionally, overexpression of TOB1-AS1 significantly inhibited cell proliferation, cell cycle progression, invasion and induced apoptosis, while knockdown of TOB1-AS1 exhibited the opposite effect. Furthermore, it was determined that TOB1-AS1 was able to bind and degrade the expression of miR-27b. Upregulation of miR-27b promoted cell growth, cell cycle transition from G1 phase to S phase, and invasion and reduced apoptosis, phenomenon could be reversed by TOB1-AS1. Inhibition of miR-27b attenuated the promotive effect of si-TOB1-AS1 on cellular processes. Upregulation of TOB1-AS1 also suppressed tumor growth in vivo. Clinically, methylation of TOB1-AS1 and low expression of TOB1-AS1 was significantly correlated with tumor stage and tumor size, respectively. Univariate and multivariate analyses confirmed that low level of TOB1-AS1 was an independent risk factor for death. In conclusion, we suggested that the epigenetically silenced TOB1-AS1 was unable to restrain miR-27b, which contributed to cervical cancer progression.

13.
J Biomater Sci Polym Ed ; 29(16): 1949-1963, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29920151

RESUMO

In this study, we fabricated paclitaxel (PTX) and etoposide (ETP) loaded Poly (lactic-co-glycolic acid) (PLGA) microspheres with core-shell structures and particle sizes ranging from 1 to 4 µm by coaxial electrospraying. The microspheres were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM). The drug loading rate and entrapment efficiency of the microspheres were detected by high performance liquid chromatograph (HPLC). Moreover, the drug release profiles and degradation of drug-loaded PLGA microspheres in vitro were investigated, respectively. The distinct layered structure that existed in the manufactured core-shell microspheres can be observed by TEM. The in vitro release profiles indicated that the PLGA/PTX + ETP (PLGA/PE) microspheres exhibited the controlled release of two drugs in a sequential manner. Cell Counting Kit-8 was used to detect the toxic and side effects of the microspheres on bone tumor cells. PTX and ETP for combination drug therapy loaded microspheres had more cytotoxic effect on saos-2 osteosarcoma cells than the individual drugs. In conclusion, core-shell PLGA microspheres by electrospraying for combination drug therapy is promising for medicine applications, the PLGA/PE microspheres have some potential for osteosarcoma treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Portadores de Fármacos/química , Etoposídeo/farmacologia , Paclitaxel/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Antineoplásicos Fitogênicos/toxicidade , Neoplasias Ósseas , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Interações Medicamentosas , Liberação Controlada de Fármacos , Etoposídeo/toxicidade , Humanos , Microesferas , Paclitaxel/toxicidade , Tamanho da Partícula
14.
J Mater Chem B ; 6(46): 7621-7633, 2018 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-32254884

RESUMO

Dual-drug loaded and dual-responsive core-shell particles (DD particles) were synthesized via an electrospray method in one step. First, 4-CBS-chitosan was synthesized by conjugating an aromatic sulfonamide group at the C2-N position of chitosan. Then, poly(nisopropylacylamide) (PNIPAM) containing apatinib model drug solution as the outer solution and 4-CBS-chitosan containing doxorubicin (DOX) as the inner solution were injected through a coaxial tube into a high voltage electric field. The formulation conditions of the DD particles were tuned to obtain spherical particles with narrow size distributions (94.97 ± 33.75 nm in diameter). The particles showed excellent responses to changes in pH and temperature: the releases of entrapped apatinib and doxorubicin (DOX) were accelerated when the solution temperature was above its lower critical solution temperature (LCST) (34 °C) or when the solution pH was acidic (pH 1.2). Degradation studies indicated that the DD particles degraded; the inner layer sank and the outer layer fragmented. In vivo biodistribution was studied by intragastric administration; it was found that the retention time of the drugs in the stomach was significantly improved and the initial burst release decreased, while a higher drug concentration level was maintained for a long time. These particles can exploit triggering mechanisms for release of the entrapped drugs from the particles, indicating their great potential for use in controlled release applications.

15.
Oncotarget ; 8(35): 59570-59580, 2017 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-28938660

RESUMO

BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) in sarcoma remains controversial. We performed a meta-analysis so as to investigate the impact of PD-L1 on clinicopathlogical findings and survival outcomes in sarcoma. MATERIALS AND METHODS: A comprehensive search in PubMed, Embase and the Cochrane Library was conducted for relevant studies. The odds ratios or hazard ratios, at 95% confidence intervals were used as measures for investigation of the correlation between PD-L1 expression and clinicopathlogical features or survival outcomes. RESULTS: Fourteen eligible studies comprising 868 patients were selected for analysis. Pooled hazard ratios indicated that the association of PD-L1 expression with overall survival in bone sarcoma (osteosarcoma and chondrosarcoma) patients was statistically significant (1.987, 95% CI: 1.224-3.224, p = 0.005), as was its association with event-free survival in bone and soft-tissue sarcoma patients (3.868, 95% CI: 2.298-6.511, p = 0.000). Additionally, the expression of PD-L1 was positively correlated with the infiltration of programmed death 1 (PD-1) positive T-lymphocytes (OR: 4.012, 95% CI: 2.391-6.733, p = 0.000). CONCLUSIONS: Our meta-analysis indicated that high PD-L1 expression is likely to be a negative factor for patients with sarcomas and that it predicts worse survival outcomes.

16.
J Exp Clin Cancer Res ; 35(1): 161, 2016 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-27716441

RESUMO

BACKGROUND: Osteosarcoma is the most prevalent primary malignant bone tumor, but treatment is difficult and prognosis remains poor. Recently, large-dose chemotherapy has been shown to improve outcome but this approach can cause many side effects. Minimizing the dose of chemotherapeutic drugs and optimizing their curative effects is a current goal in the management of osteosarcoma patients. METHODS: In our study, trypan blue dye exclusion assay was performed to investigate the optimal conditions for the sensitization of osteosarcoma U2OS cells. Cellular uptake of the fluorophores Lucifer Yellow CH dilithium salt and Calcein was measured by qualitative and quantitative methods. Human MTX ELISA Kit and MTT assay were used to assess the outcome for osteosarcoma U2OS cells in the present of shock wave and methotrexate. To explore the mechanism, P2X7 receptor in U2OS cells was detected by immunofluorescence and the extracellular ATP levels was detected by ATP assay kit. All data were analyzed using SPSS17.0 statistical software. Comparisons were made with t test between two groups. RESULTS: Treatment of human osteosarcoma U2OS cells with up to 450 shock wave pulses at 7 kV or up to 200 shock wave pulses at 14 kV had little effect on cell viability. However, this shock wave treatment significantly promoted the uptake of Calcein and Lucifer Yellow CH by osteosarcoma U2OS cells. Importantly, shock wave treatment also significantly enhanced the uptake of the chemotherapy drug methotrexate and increased the rate of methotrexate-induced apoptosis. We found that shock wave treatment increased the extracellular concentration of ATP and that KN62, an inhibitor of P2X7 receptor reduced the capacity methotrexate-induced apoptosis. CONCLUSIONS: Our results suggest that shock wave treatment promotes methotrexate-induced apoptosis by altering cell membrane permeability in a P2X7 receptor-dependent manner. Shock wave treatment may thus represent a possible adjuvant therapy for osteosarcoma.


Assuntos
Trifosfato de Adenosina/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Neoplasias Ósseas/metabolismo , Metotrexato/farmacologia , Osteossarcoma/metabolismo , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Tratamento por Ondas de Choque Extracorpóreas , Fluoresceínas/metabolismo , Humanos , Osteossarcoma/terapia , Receptores Purinérgicos P2X7/metabolismo
17.
Oncol Rep ; 35(3): 1645-51, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26706910

RESUMO

Dysregulation of microRNAs (miRNAs) occurs frequently in cervical carcinogenesis. miRNAs function as tumor-suppressors or oncogenes and are involved in tumor behavior. However, the expression and function of miR-27b in cervical carcinogenesis remain unknown. In the present study, we observed that miR-27b was significantly increased in cervical cancer cells and tissues, and upregulation of miR-27b was negatively associated with its direct target, cadherin 11 (CDH11). Upregulation of miR-27b significantly accelerated the proliferation, cell cycle transition from G1 to S phase, migration and invasion of C33A cells, while downregulation of miR-27b suppressed the proliferation and invasion of HeLa cells. Moreover, CDH11 cDNA transfection impaired the oncogenic effect of miR-27b on cancer cells. Knockdown of CDH11 attenuated the suppressive effect of an miR-27b inhibitor on cervical cancer cells. In addition, we found that CDH11 was involved in miR-27b-induced epithelial-mesenchymal transition (EMT) by regulating expression of E-cadherin, vimentin and N-cadherin. Our results for the first time indicate that miR-27b acting as an oncogene may play an important role in the progression of cervical cancer by modulating CDH11 and EMT.


Assuntos
Caderinas/biossíntese , Carcinogênese/genética , MicroRNAs/genética , Neoplasias do Colo do Útero/genética , Caderinas/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , MicroRNAs/biossíntese , Invasividade Neoplásica/genética , Neoplasias do Colo do Útero/patologia
18.
J Craniofac Surg ; 26(7): 2180-3, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26468807

RESUMO

The aim of this study was to measure the related parameters of the cochlea, so as to allow preoperative assessment of the anatomic relationship of the petrous internal carotid artery (ICA), the facial nerve (FN), and the cochlea during skull base surgery. Seven parameters of these 3 structures were examined in the computed tomographic scan of 120 patients. The shortest distance from the cupula cochleae to the petrous ICA and the FN is as follows: 19.39 (1.01) mm to the stylomastoid foramen (D2), 10.27 (0.80) mm to the midpoint of the genu of FN canal (D3), 13.66 (0.88) mm to the exocranial opening of the carotid canal (D4), and 5.64 (1.03) mm to the midpoint of carotid knee (D5). The shortest distance between the mastoid segment of FN canal and the vertical segment of the petrous ICA (D6) was 13.33 (1.25) mm. The angle between D2 and D3 was measured at 45.66 (3.31)°, and the angle between D4 and D5 was measured at 41.08 (2.64)°. Clinically, it is relatively safe to work within the distances and angles measured in this research, and these results may give surgeons a practical and specific view of these 3 structures in the skull base approaches such as anterior transpetrosal approach to achieve the best possible surgical outcome and maximize safety.


Assuntos
Artéria Carótida Interna/anatomia & histologia , Cóclea/anatomia & histologia , Nervo Facial/anatomia & histologia , Osso Petroso/cirurgia , Adulto , Variação Anatômica , Artéria Carótida Interna/diagnóstico por imagem , Cefalometria/métodos , Cóclea/diagnóstico por imagem , Nervo Facial/diagnóstico por imagem , Feminino , Tomografia Computadorizada Quadridimensional/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Processo Mastoide/anatomia & histologia , Pessoa de Meia-Idade , Segurança do Paciente , Osso Petroso/irrigação sanguínea , Osso Petroso/inervação , Base do Crânio/cirurgia , Tomografia Computadorizada Espiral/métodos , Adulto Jovem
19.
Oncol Rep ; 33(5): 2337-44, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25813398

RESUMO

The ATPase family AAA domain-containing protein 2 (ATAD2) is associated with many cellular processes, such as cell proliferation, invasion and migration. However, the molecular biological function of the ATAD2 gene in cervical cancer is unclear. The purpose of this study was to explore ATAD2 expression in cervical cancer, evaluate the relationship between the development of cervical cancer, metastasis and clinicopathological characteristics, and discuss the implications for its use in clinical treatment. Protein and mRNA expression of ATAD2 was examined in tissues and cell lines. Tumor tissues from 135 cases of cervical cancer were collected for evaluation of ATAD2 expression by immunohistochemistry and western blotting. Prognostic significance was evaluated by the Cox hazards model and Kaplan-Meier survival method. HeLa and SiHa cells were transfected with two siRNAs targeting ATAD2. ATAD2 knockdown was used to analyze cell proliferation, invasion and migration. Cell viability was evaluated with the Cell Counting Κit-8 (CCK-8) assay, cell invasion by a Transwell assay and cell migration by a wound healing/scratch migration assay. ATAD2 was shown to be highly expressed in cervical cancer tissues, both at the transcriptional and protein levels, and was correlated with poor patient survival (P<0.05). Knockdown of ATAD2 in the HeLa and SiHa cells was found to reduce the capacity for invasion and migration (P<0.05), and inhibited the growth and clonogenic potential of the HeLa and SiHa cell lines. Our results suggest that cervical cancer tissues may have highly expressed ATAD2, which is associated with tumor stage and lymph node status (P<0.05). Oncogene ATAD2 may play an important role in cervical cancer proliferation, invasion and migration. It could serve as a prognostic marker and a therapeutic target for cervical cancer.


Assuntos
Adenocarcinoma/genética , Adenosina Trifosfatases/genética , Carcinoma de Células Escamosas/genética , Proteínas de Ligação a DNA/genética , RNA Mensageiro/metabolismo , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , ATPases Associadas a Diversas Atividades Celulares , Adenocarcinoma/patologia , Adulto , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Células HeLa , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/patologia
20.
J Craniofac Surg ; 24(2): 614-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23524757

RESUMO

Facial nerve (FN) paralysis is a rare but devastating complication of cochlear implant surgery. This study aimed to measure the cupula of the cochlea to the tympanic segment of the FN canal, cupula of the cochlea to the mastoid segment of the FN canal, and the geniculate ganglion to provide a more secure and accurate orientation of the FN canal and to facilitate operation on the cochlea by avoiding potential damage to FN. Using computed tomography, we scanned skulls of 120 volunteers who suffer no cases of skull base lesions. Multiplane reconstruction images were prepared with high-resolution computed tomography. Preoperative evaluation of the FN anatomy within the temporal bone by high-resolution computed tomography helps in minimizing surgical trauma to the nerve, and these results can help guide clinical surgery on the cochlea.


Assuntos
Cóclea/diagnóstico por imagem , Nervo Facial/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Osso Temporal/diagnóstico por imagem
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