RESUMO
Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine-zinc (DPA-Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape.
Assuntos
Neoplasias , Zinco , Ligação Proteica , Polímeros/metabolismo , DNA/metabolismo , Cátions , Transfecção , Técnicas de Transferência de Genes , Polietilenoglicóis/metabolismo , Neoplasias/terapiaRESUMO
BACKGROUND: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma. This study compared the effects of BT and cryoballoon ablation (CBA) therapy on the airway smooth muscle (ASM). METHODS: Eight healthy male beagle dogs were included in this experiment. In the preliminary experiment, one dog received BT treatment for both lower lobe bronchus, another dog received CBA treatment for 7 s on the upper and lower lobe of right bronchus, and 30 s on the left upper and lower lobe. The treatments were performed twice at an interval of 1 month. In subsequent experiments, the right lower lobe bronchus was treated with BT, and the left lower lobe bronchus was treated with CBA. The effects of treatment were observed after 1 (nâ=â3) month and 6 months (nâ=â3). Hematoxylin-eosin staining, Masson trichrome staining, and immunohistochemical staining were used to compare the effects of BT and CBA therapy on the ASM thickness, collagen fibers synthesis, and M3 receptor expression after treatment. One-way analysis of variance with Dunnett post hoc test was used to analyze the differences among groups. RESULTS: In the preliminary experiment, the ASM ablation effect of 30-s CBA was equivalent to that of 7-s CBA (ASM thickness: 30.52â±â7.75âµm vs. 17.57â±â15.20âµm, Pâ=â0.128), but the bronchial mucociliary epithelium did not recover, and large numbers of inflammatory cells had infiltrated the mucosal epithelium at 1-month post-CBA with 30-s freezing. Therefore, we chose 7 s as the CBA treatment time in our follow-up experiments. Compared with the control group (35.81â±â11.02âµm), BT group and CBA group (13.41â±â4.40âµm and 4.81â±â4.44âµm, respectively) had significantly decreased ASM thickness after 1 month (Pâ<â0.001). Furthermore, the ASM thickness was significantly lower in the 1-month post-CBA group than in the 1-month post-BT group (Pâ=â0.015). There was no significant difference in ASM thickness between the BT and CBA groups after six months (9.92â±â4.42âµm vs. 7.41â±â7.20âµm, Pâ=â0.540). Compared with the control group (0.161â±â0.013), the average optical density of the ASM M3 receptor was significantly decreased in 6-month post-BT, 1-month post-CBA, and 6-month post-CBA groups (0.070â±â0.022, 0.072â±â0.012, 0.074â±â0.008, respectively; all Pâ<â0.001). There was no significant difference in the average optical density of ASM M3 receptor between the BT and CBA therapy groups after six months (Pâ=â0.613). CONCLUSIONS: CBA therapy effectively ablates the ASM, and its ablation effect is equivalent to that of BT with a shorter onset time. A neural mechanism is involved in both BT and CBA therapy.
Assuntos
Termoplastia Brônquica , Criocirurgia , Animais , Brônquios/cirurgia , Broncoscopia , Cães , Humanos , Masculino , Músculo LisoRESUMO
Polymerization-induced self-assembly has been demonstrated to be a powerful strategy for fabricating polymeric nanoparticles in the last two decades. However, the stringent requirements for the monomers greatly limit the chemical versatility of PISA-based functional nanoparticles and expanding the monomer family of PISA is still highly desirable. Herein, a camptothecin analogue (CPTM) is first used as the monomer in PISA. Prodrug nanoparticles with reduction-responsive camptothecin release behavior are fabricated at 10% solid concentration (100 mg g-1 ). Poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) are used as the macro RAFT agents to comediate the RAFT dispersion polymerization of CPTM in ethanol to produce the PHPMA/PDEAEMA-stabilized nanoparticles. The PDEAEMA chains become hydrophobic and are in the collapsed state at physiological pH values. In contrast, in the vicinity of an acidic tumor, the tertiary amine groups of PDEAEMA chains are rapidly protonated, leading to fast hydrophobic-hydrophilic transitions and charge reversal. Such fast charge-reversal results in enhanced cancer cell internalization of the prodrug nanoparticles, thus achieving superior anticancer efficacy.
Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Pró-Fármacos/química , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Etanol/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Metacrilatos/química , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Nylons/química , Polimerização , Polímeros/química , Ácidos Polimetacrílicos/química , Água/químicaRESUMO
Mesencephalic astrocytederived neurotrophic factor (MANF) is an endoplasmic reticulum stressinducible protein, which has been suggested to be upregulated in inflammatory diseases; however, how inflammation regulates its transcription remains unclear. Activator protein1 (AP1), which is a transcription factor complex composed of cFos and cJun, is activated during the inflammatory process. The present study aimed to investigate whether the AP1 complex regulates MANF transcription. The results of a luciferase reporter assay revealed that one of three putative AP1 binding sites in the MANF promoter region is essential for enhancement of MANF transcription. Mechanistically, AP1 was revealed to directly bind to the promoter region of the MANF gene by chromatin immunoprecipitation assay. Furthermore, MANF was strongly expressed in the liver tissues of patients with hepatitis B virus (HBV) infection, compared with in normal liver tissues from patients with hepatic hemangioma. Furthermore, cFos and cJun were also upregulated in the nuclei of hepatocytes from patients with HBV infection. In mice treated with carbon tetrachloride, the expression patterns of MANF, cFos and cJun were similar to those in patients with HBV. These results suggested that the AP1 complex may be a novel regulator of MANF transcription, which may be involved in liver inflammation and fibrosis.
Assuntos
Regulação da Expressão Gênica , Fatores de Crescimento Neural/genética , Fator de Transcrição AP-1/metabolismo , Transcrição Gênica , Animais , Sequência de Bases , Sítios de Ligação , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Ligação ProteicaRESUMO
Glioblastoma (GBM) is the most commonly diagnosed solid tumor outside the central nervous system. However, genetic factors underlying GBM remain largely unclear. Previous studies indicated that Glial fibrillary acidic protein (GFAP) might play an important role in the aggressiveness of GBM and also contributed to its poor overall survival. The present study aims to test (1) the associations between GFAP single nucleotide polymorphisms (SNPs) and GBM cells chemoresistance and metastasis, and (2) the molecular mechanism accounting for their effects. Four tagging SNPs of GFAP were initially genotyped in 667 subjects and the significant SNP was further analyzed via online bioinformatical tools. SNP rs11558961 was found to be significantly associated with GBM susceptibility. It was predicted to influence microRNA(miR)-139 binding to 3'UTR of GFAP gene. In functional experiments, we found that cells transfected with rs11558961 G-allele constructs had lower baseline luciferase activities and were more responsive to miR-139 changes, compared to C-allele constructs. Moreover, rs11558961 C>G variant reduced the chemoresistance of GBM cells and migration capability. In conclusion, rs11558961 might influence the chemoresistance and progression of GBM cells via promoting the binding of miR-139, ultimately decrease the susceptibility of GBM. This investigation will shed light on the optimizing for clinical trial design and individualizing of therapeutic plans.
Assuntos
Neoplasias Encefálicas/genética , Predisposição Genética para Doença/genética , Proteína Glial Fibrilar Ácida/genética , Glioblastoma/genética , MicroRNAs/metabolismo , Adulto , Idoso , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genótipo , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Grazing is one of the most important ways for managing grassland in northern China. Different studies have focused on the effects of grazing on the structure and function of ecosystems. Grazing affects the structure and function of soil via biological and physical processes, such as animal trampling, feeding, and excretion, which further affects N2O emissions. However, there is less research on greenhouse gases (GHGs) emissions by grazing intensities in semi-arid grassland ecosystems in northern China. In this study, four different grazing intensities were considered in the semi-arid grassland ecosystem of the typical agro-pastoral ecotone in northern China (Youyu, Shanxi). The influence of different grazing intensities on GHG fluxes was studied by measuring GHGs fluxes in the growing season with an opaque static chamber. The results showed that â Grazing had no effect on CO2 and N2O fluxes during the first year of grazing treatment. â¡ However, grazing decreased soil water content (P<0.05), moderate grazing intensity decreased microbial biomass carbon (P<0.05), and moderate and heavy grazing intensities reduced microbial biomass nitrogen (P<0.05). ⢠Significant positive correlations between CO2 flux and soil temperature and soil moisture were observed. The correlation between temperature and CO2 emissions was increased by grazing. ⣠There was a significant positive correlation between soil temperature, soluble nitrogen, soil microbial biomass nitrogen, CO2 flux, and N2O flux. Our results indicated that GHG, regulated by soil microorganisms, was affected by soil temperature and moisture.
Assuntos
Pradaria , Gases de Efeito Estufa/análise , Herbivoria , Microbiologia do Solo , Animais , Dióxido de Carbono/análise , China , Gado , Nitrogênio/análise , Óxido Nitroso/análise , Solo , Temperatura , ÁguaRESUMO
Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane. Recent studies showed that TMEM88 was involved in the regulation of several types of cancer. TMEM88 was expressed at significantly higher levels in breast cancer (BC) cell line than in normal breast cell line with co-localized with Dishevelled (DVL) in the cytoplasm of BC cell line. TMEM88 silencing in the ovarian cancer cell line CP70 resulted in significant upregulation of Wnt downstream genes (c-Myc, cyclin-D1) and other Wnt target genes including JUN, PTIX2, CTNNB1 (ß-catenin), further supporting that TMEM88 inhibits canonical Wnt signaling pathway. Wnt signaling pathway has been known to play important roles in many diseases, especially in cancer. For instance, hepatocellular carcinoma (HCC) has become one of the most common tumors harboring mutations in the Wnt signaling pathway. As the inhibitor of Wnt signaling, TMEM88 has been considered to act as an oncogene or a tumor suppressor. Up-regulated TMEM88 or gene therapy approaches could be an effective therapeutic approach against tumor as TMEM88 inhibits Wnt signaling through direct interaction with DVL. Here, we review the current knowledge on the functional role and potential clinical application of TMEM88 in the control of various cancers. Highlights Wnt signaling displays an important role in several pathogenesis of cancer. Wnt signaling pathway is activated during cancer development. TMEM88 has an impact on cancer by inhibiting canonical Wnt signaling. We discuss the importance and new applications of TMEM88 in cancer therapy.
Assuntos
Transformação Celular Neoplásica/metabolismo , Proteínas de Membrana/metabolismo , Neoplasias/metabolismo , Via de Sinalização Wnt , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Progressão da Doença , Proteínas Desgrenhadas/genética , Proteínas Desgrenhadas/metabolismo , Regulação Neoplásica da Expressão Gênica , Terapia Genética/métodos , Humanos , Proteínas de Membrana/genética , Neoplasias/genética , Neoplasias/patologia , Neoplasias/terapiaRESUMO
Small guanosine triphosphate (GTP)-binding protein RhoB is an important stress sensor and contributes to the regulation of cytoskeletal organization, cell proliferation and survival. However, whether RhoB is involved in the hypoxic response and action of glucocorticoid (GC) is largely unknown. In this study, we investigated the effects of hypoxia or/and GC on the expression and activition of RhoB in the lung of rats and human A549 lung carcinoma cells, and further studied its mechanism and significance. We found that hypoxia and dexamethasone (Dex), a synethic GC, not only significantly increased the expression and activation of RhoB independently but also coregulated the expresion of RhoB in vitro and in vivo. Up-regulation of RhoB by hypoxia was in part through stabilizing the RhoB mRNA and protein. Inhibiting hypoxia-activated hypoxia-inducible transcription factor-1α (HIF-1α), c-Jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) with their specific inhibitors significantly decreased hypoxia-induced RhoB expression, indicating that HIF-1α, JNK and ERK are involved in the up-regulation of RhoB in hypoxia. Furthermore, we found that knockdown of RhoB expression by RhoB siRNA not only significantly reduced hypoxia-enhanced cell migration and cell survival in hypoxia but also increased the sensitivity of cell to paclitaxel (PTX), a chemotherapeutic agent, and reduced Dex-enhanced resistance to PTX-chemotherapy in A549 cells. Taken together, the novel data revealed that hypoxia and Dex increased the expression and activation of RhoB, which is important for hypoxic adaptation and hypoxia-accelerated progression of lung cancer cells. RhoB also enhanced the resistance of cell to PTX-chemotherapy and mediated the pro-survival effect of Dex.
Assuntos
Glucocorticoides/farmacologia , Pulmão/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteína rhoB de Ligação ao GTP/metabolismo , Células A549 , Animais , Antineoplásicos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Hipóxia Celular/genética , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dexametasona/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Pulmão/efeitos dos fármacos , Modelos Biológicos , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteína rhoB de Ligação ao GTP/genéticaRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) came out to attract wide attention and had become one of the hotspots of most diseases' research in decades. But at present, the mechanisms of how MSCs work on chronic asthma remain undefined. Our study aims at verifying whether MSCs play a role in preventing inflammation and airway remodeling via PI3K/AKT signaling pathway in the chronic asthma rats model. METHODS: First, an ovalbumin (OVA)-induced asthma model was built. MSCs were administered to ovalbumin-induced asthma rats. The total cells in a bronchial alveolar lavage fluid (BALF) and inflammatory mediators in BALF and serum were measured. Histological examination of lung tissue was performed to estimate the pathological changes. Additionally, the expression of phosphorylated-Akt (p-Akt) in all groups was measured by western blot and immunohistochemistry (IHC). RESULTS: Compared to normal control group, the degree of airway inflammation and airway remodeling was significantly increased in asthma group. On the contrary, they were obviously inhibited in MSCs transplantation group. Moreover, the expression of p-Akt was increased in lung tissues of asthmatic rats, and suppressed by MSCs transplantation. CONCLUSION: Our results demonstrated that MSCs transplantation could suppress lung inflammation and airway remodeling via PI3K/Akt signaling pathway in rat asthma model.
Assuntos
Remodelação das Vias Aéreas/fisiologia , Asma/metabolismo , Pulmão/metabolismo , Transplante de Células-Tronco Mesenquimais , Fosfatidilinositol 3-Quinases/metabolismo , Pneumonia/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Asma/induzido quimicamente , Asma/patologia , Asma/terapia , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Pulmão/patologia , Masculino , Ovalbumina , Pneumonia/induzido quimicamente , Pneumonia/patologia , Pneumonia/terapia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologiaRESUMO
This study was designed to establish a biomarker risk model for predicting brain metastasis (BM) in non-small cell lung cancer (NSCLC). The model comprises 120 cases of NSCLC that were treated and followed up for 4 years. The patients were divided into the BM (n=50) and non-BM (other visceral metastasis and those without recurrence) (n=70) groups. Immunohistochemical and western blot analyses were performed in metastatic tissues of NSCLC. Multivariate regression analysis was performed to correlate the immunoreactive cyclase-associated protein 1 (CAP1) signal with BM. Survival analyses were performed by using the Kaplan-Meier method. CAP1 protein content and immunoreactivity were significantly increased in BM specimens compared to other-metastatic specimens. The survival analysis revealed that CAP1 overexpression was significantly associated with survival (P<0.05). The ROC test suggested that the area under the curve was 73.33% (P<0.001; 95% CI, 63.5-83.2%). When P=0.466, the sensitivity and specificity reached 79.5 and 67.1%, respectively. These findings suggested that CAP1 is involved in the BM of NSCLC, and that elevated levels of CAP1 expression may indicate a poor prognosis for patients with BM. The CAP1 molecular model may be useful in the prediction of the risk of BM in NSCLC.
Assuntos
Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/metabolismo , Proteínas do Citoesqueleto/metabolismo , Neoplasias Pulmonares/patologia , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Estudos de Casos e Controles , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/genética , Proteínas do Citoesqueleto/análise , Proteínas do Citoesqueleto/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Análise de Regressão , Análise de SobrevidaRESUMO
OBJECTIVE: To investigate the relationship between expression of matrix metalloproteinase (MMP)-9 and expression of adenylyl cyclase-associated protein (CAP)-1 in chronic obstructive pulmonary disease (COPD). METHODS: Patients with possible respiratory disease were recruited into the study and divided into a COPD group and a non-COPD group on diagnosis. Pulmonary function tests were performed and serum concentrations of MMP-9 were measured using an enzyme-linked immunosorbent assay. MMP-9 and CAP1 expression were analysed in lung tissue and bronchoalveolar lavage fluid in all available samples using immunohistochemistry and Western blot, respectively. In addition, expression of MMP-9 and CAP1 in vitro was investigated using immunofluorescence. Expression of CAP1 in response to MMP-9 was measured in the human alveolar epithelial cell line HP-AEpiC, using Western blot. RESULTS: A total of 90 patients were included in the study: 52 were in the COPD group and 38 in the non-COPD group. Serum MMP-9 concentrations were significantly higher in the COPD than in the non-COPD group. MMP-9 serum concentrations were negatively correlated with forced expiratory volume in 1 s (FEV1), FEV1 as a percentage of the normal predicted value and the ratio of FEV1 to forced vital capacity, and were positively correlated with residual volume (RV), total lung capacity (TLC) and RV/TLC values. In lung tissue and bronchoalveolar lavage fluid samples, MMP-9 and CAP1 expression were inversely related. This relationship was confirmed in HP-AEpiC cells. High expression of MMP-9 and low expression of CAP1 was demonstrated in the COPD group compared with the non-COPD group. CONCLUSIONS: This study demonstrated an inverse relationship between CAP1 and MMP-9 expression, and high expression of MMP-9 and low expression of CAP1 in those with COPD compared with the non-COPD group. Overexpression of MMP-9 in lung tissue and its interaction with CAP1 is likely to play a major role in airway obstruction in COPD.
Assuntos
Adenilil Ciclases/biossíntese , Proteínas de Ciclo Celular/biossíntese , Proteínas do Citoesqueleto/biossíntese , Metaloproteinase 9 da Matriz/sangue , Doença Pulmonar Obstrutiva Crônica/metabolismo , Adenilil Ciclases/genética , Líquido da Lavagem Broncoalveolar/química , Proteínas de Ciclo Celular/genética , Linhagem Celular , Proteínas do Citoesqueleto/genética , Células Epiteliais/metabolismo , Volume Expiratório Forçado/fisiologia , Humanos , Pulmão/metabolismo , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , Doença Pulmonar Obstrutiva Crônica/genética , Testes de Função Respiratória , Mucosa Respiratória/metabolismo , Capacidade Pulmonar Total/fisiologiaRESUMO
PURPOSE: To determine the role of brain metastases (BM) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) by performing a meta-analysis of the RCTs (randomized controlled clinical trials) and non-RCTs (non-randomized controlled clinical trials) published in the literature. METHODS: A meta-analysis was performed using trials identified through PubMed, EMBASE and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included BM, OS, median survival (MS), response rate (RR), Hazard ratios (HRs) and odds ratios (ORs), and their 95% confidence intervals (CIs) were pooled using ReMan software. RESULTS: Twelve trials (6 RCTs and 6 non-RCTs) involving 1,718 NSCLC patients met the inclusion criteria. They were grouped on the basis of study design for separate Meta-analyses. The results showed that prophylactic cranial irradiation (PCI) reduced the risk of BM as compared with non-PCI in NSCLC patients (ORâ=â0.30, 95% [CI]: 0.21-0.43, p<0.00001). However, HRs for OS favored non-PCI (HRâ=â1.19, 95% [CI]: 1.06-1.33, pâ=â0.004), without evidence of heterogeneity between the studies. CONCLUSION: Our results suggest that although PCI decreased the risk of BM, it may impose a detrimental effect on OS of NSCLC patients.
Assuntos
Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Irradiação Craniana , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pré-Medicação , Estudos de Casos e Controles , Humanos , Ensaios Clínicos Controlados não Aleatórios como Assunto , Razão de Chances , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Adiposity is a well-recognized risk factor of type 2 diabetes and cardiovascular disease, and recently there is increasing evidence that excess body weight is an avoidable cause of cancer, including gastrointestinal, endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal malignancies. The mechanisms whereby adiposity is associated with tumor development remains not well understood. There are some most studied hypothesized mechanisms such as, high levels of insulin and free levels of insulin-like growth factors, sex hormones, adipocytokines, and inflammatory cytokines, adiposity-induced hypoxia, and so on. The potential mechanisms and conclusions in adiposity associated with increased risk for developing malignancy, and the underlying cellular and molecular mechanisms will be studied very well in the near future.
Assuntos
Adiposidade , Neoplasias/etiologia , Obesidade/complicações , Humanos , Neoplasias/mortalidade , Neoplasias/patologia , Obesidade/mortalidade , Obesidade/patologia , Prognóstico , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVES: To investigate the effects of adenovirus-mediated inducible nitric oxide synthase gene transfection on bladder transitional cell carcinoma T24 cells, and to provide novel insights and approaches to clinical therapies against bladder transitional cell carcinoma. METHODS: Firstly, construct recombinant adenovirus vector pAd-iNOS of iNOS, followed by transfection of pAd-iNOS into HECK293 packaging cells. Thirdly, harvest recombinant adenovirus rAd-iNOS after amplification and purification procedures. Finally, transfect the recombinant adenovirus rAd-iNOS into human bladder carcinoma T24 cells and examine the effect of rAd-iNOS transfection on apoptosis of T24 and possible mechanism. RESULTS: As shown by this study, the recombinant adenovirus rAd-iNOS was constructed successfully. The virus titer was 5.8×10(8) PFU/mL and recombinant was verified by PCR analysis. Transfection of adenovirus rAd-iNOS into T24 cells could induce secretion of high NO concentration, P53 protein expression up-regulation, as well as promotion of T24 cell apoptosis. CONCLUSIONS: The transfection of human bladder carcinoma T24 cells from recombinant adenovirus rAd-iNOS was confirmed to induce intracellular iNOS over-expression, high production of NO, up-regulation of intracellular P53 expression and promotion of cell apoptosis.
RESUMO
OBJECTIVE: To investigate the role of the HoxA13 gene from the HOX family in the development of hypospadias by detecting the transcription and expression of HoxA13 in the prepuce and urethral plate of hypospadias patients. METHODS: We collected the tissues from the prepuce and urethral plate of 30 hypospadias patients aged 3.3 - 11.6 years, the prepuce of 10 phimosis children aged 3.1 - 10.4 years and the urethra of 10 penile carcinoma patients aged 48.1 - 75.6 years with no urethral involvement, the latter 20 taken as controls. We divided the tissue samples into a distal, an intermedial, a proximal and a control group, and detected the expressions of HoxA13 mRNA and protein in different groups by RT-PCR and immunohistochemistry. RESULTS: RT-PCR showed that the HoxA13 mRNA expressions in the prepuce and urethral plate were significantly higher in the control group (1.409 +/- 0.441 and 1.270 +/- 0.209) than in the intermedial (0.848 +/- 0.338 and 0.684 +/- 0.228) and proximal group (0.497 +/- 0.218 and 0.464 +/- 0.164) (P < 0.05 or P < 0.01), and so were they in the distal (1.071 +/- 0.342 and 1.054 +/- 0.189) than in the proximal group (P < 0.05). Immunohistochemistry revealed that the HoxA13 protein expressions in the prepuce and urethral plate were remarkably higher in the control group (12 050 +/- 4 112 and 13 420 +/- 2 636) than in the intermedial (5 217 +/- 1 993 and 5 238 +/- 3 065) and proximal group (2 095 +/- 1 591 and 2 238 +/- 2 217) (P < 0.05 or P < 0.01), and so were they in the distal (8 223 +/- 3 212 and 10 450 +/- 2 123) than in the proximal group (P < 0.05). CONCLUSION: The transcription and expression of HoxA13 in the prepuce and urethral plate of hypospadias patients are closely related with the abnormal position of the urethral meatus, and their abnormal expressions may affect the development and formation of the urethra.
Assuntos
Prepúcio do Pênis/metabolismo , Proteínas de Homeodomínio/metabolismo , Hipospadia/metabolismo , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Proteínas de Homeodomínio/genética , Humanos , Hipospadia/genética , Masculino , Pessoa de Meia-Idade , Uretra/metabolismoRESUMO
Myopericytoma is a benign tumor composed of cells that show apparent differentiation towards putative perivascular myoid cells called myopericytes. To date, only a small number of series describing myopericytomas have been reported. Here, we report a case of pulmonary myopericytoma presenting as multiple nodules in a 26-year-old man. Clinical presentation, radiological features and histopathologic findings of the patient are also discussed. The result of the histology combined with the immunohistochemical analysis led to a diagnosis of myopericytomas. To our knowledge, this is the first report of myopericytoma showing pulmonary involvement.
Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Pericitos/patologia , Neoplasias de Tecidos Moles/diagnóstico , Actinas/análise , Adulto , Antígenos CD34/análise , Biomarcadores Tumorais/análise , Biópsia , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Imageamento por Ressonância Magnética , Masculino , Neoplasias Primárias Múltiplas/química , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Pneumonectomia , Neoplasias de Tecidos Moles/química , Neoplasias de Tecidos Moles/diagnóstico por imagem , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/cirurgia , Tomografia Computadorizada por Raios X , Vimentina/análiseRESUMO
BACKGROUND: Microwaves have other biological effects on cancer as well besides killing tumor cells by coagulation. Some studies showed that microwaves may induce apoptosis in some tumor cells. The apoptotic effect of microwaves may help in clinic to remove residual malignant cells nearby the primary lesion and avoid relapse subsequently. However, there is little evidence on this subject from lung cancer. We studied the effect of microwaves on inducing apoptosis in the human lung carcinoma cell line A549 cells, aiming to identify its effect on apoptosis. METHODS: A549 cells were radiated by various intensities and durations of microwaves. Apoptosis induction in A549 cells was analyzed by morphological observations, tetrazolium blue color method (MTT) assays, flow cytometry, immunohistochemistry, and image analyses. RESULTS: Morphological changes in A549 cells, including cell shrinking and nuclear pyknosis, were observed after microwave radiation. Microwaves significantly inhibited metabolic activities and induced apoptosis in A549 cells. The results of the MTT assay showed a significant decrease of cell activities in all the radiation groups compared with the normal control (P < 0.01). The low point of cell activities often appeared at 6 - 12 hours after radiation. Apoptosis was also confirmed by flow cytometry. The early stage apoptotic rate reached 6.10% - 17.98% and the advanced stage apoptotic rate + necrosis rate reached 8.04% - 44.06% at 6 hours after microwave irradiation, in contrast to 2.32% and 4.10% in the respective control groups. Down-regulation of Bcl-2 expression and up-regulation of p53 expression were observed by immunohistochemistry after radiation. In most treated groups, the down-regulation of Bcl-2 expression reached its lowest level at 3 - 6 hours after radiation (integrated optical density (IOD)-6 hours: 2.13 ± 0.08 - 5.14 ± 0.13 vs. control: 5.79 ± 0.10, P < 0.01) and the up-regulation of P53 expression peaked at about 3 hours (IOD-3 hours: 2.61 ± 0.13 - 8.07 ± 0.11 vs. control: 1.29 ± 0.07, P < 0.01). Cell damage, apoptosis, and protein expression levels in the samples differed depending on the radiation intensity and duration. CONCLUSIONS: Microwaves can promote apoptosis in A549 cells. The effect depends on the duration and dosage of microwave radiation. Bcl-2 and p53 proteins may be involved in the apoptotic process of A549 cells induced by microwaves.
Assuntos
Apoptose/efeitos da radiação , Neoplasias Pulmonares/metabolismo , Micro-Ondas , Linhagem Celular Tumoral , Humanos , Imuno-Histoquímica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
OBJECTIVE: To highlight the characteristics of diffuse panbronchiolitis (DPB). METHOD: One patient with DPB confirmed by thorocoscopic biopsy was described and relevant literatures were reviewed. RESULTS: DPB is a chronic lower respiratory tract disease common in Japanese, rare in China, characterized by infiltration of inflammatory cells around bronchioles. Although the etiology and precise mechanisms are under investigation, it is commonly hypothesized that heredity and immunity have a major role in DPB. Symptoms include cough, expectoration, and dyspnea after exercises. Pseudomonas aeruginosa is isolated from sputum in some cases. If left untreated, DPB progresses rapidly and has a poor prognosis if respiratory failure occurs. CONCLUSIONS: DPB should be included in the differential diagnosis of bilateral multiple pulmonary nodular shadows. Long-term, low-dose macrolide therapy may improve the prognosis through an anti-inflammatory effect.