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1.
Int J Colorectal Dis ; 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32016599

RESUMO

OBJECTIVE: Anastomotic leakage (AL) is a catastrophic surgical complication affecting the prognosis of patients after colorectal surgery. We aimed to determine the value of the arterial calcification (AC) score in predicting AL. METHODS: Medline and Embase were searched through November 2019. The odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association between AC and AL after colorectal surgery. The fixed-effects model or random-effects model was adopted for data pooling. Subgroup analyses were conducted to assess the effect of different aortoiliac trajectories. RESULTS: Four studies involving 496 patients were included. The calcium volume and calcium score measurements of different trajectories revealed a significant difference with regard to the left and right common iliac arteries, the superior mesenteric artery, and the left common iliac artery. Calcification of the internal iliac artery significantly increased the risk of AL compared with no AL (OR = 1.005; 95% CI 1.002-1.009; P = 0.005), as did calcification of the left internal iliac artery (OR = 1.009; 95% CI 1.002-1.016; P = 0.011), but not of the common iliac artery (OR = 1.001; 95% CI 1.000-1.001; P = 0.317) or common and internal iliac artery (OR = 1.000; 95% CI 1.000-1.000; P = 1.000). CONCLUSIONS: AC is associated with increased risk of AL following colorectal surgery. TRIAL REGISTRATION: CRD42019141236.

2.
J Photochem Photobiol B ; 197: 111534, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279897

RESUMO

In the search for developing a biomedicine based nanomaterial for therapeutic applications, here we described a new benign development of Photo-triggered Gold nanodots capped mesoporous silica nanoparticles Au@MSNs loaded with capsaicin (Cap) for photothermal therapy of cancer cells. Electron microscopic techniques (SEM and TEM) studies depict the anisotropic shape of Cap-Au@MSNs with mean size ≈110 nm. The successful amine functionalization and covalent interaction of Au nanodots on the mesoporous silica surface were confirmed from the results of FTIR, XPS and UV-vis spectral analyses, which directly indicates the composition of synthesized mesoporous silica surface. Additionally, Dynamic Light Scattering (DLS) revealed that synthesized cap-AuMSNs were stable with highly negatively charged. Cap-AuMSNs exhibited extraordinary in vitro antitumor activity against the tested twp thyroid cancer cell lines (i.e., FTC-133 and B-CPAP). 3-(4, 5-Dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay determined that capsaicin and Cap-AuMSNs conferred strong cytotoxicity against the FTC-133 and B-CPAP cell lines. Further, evaluation of the mechanism showed that anticancer activity was achieved by inducing apoptosis in thyroid cancer cells. In addition, we found that such compounds exhibited promising antimetastatic activity and reduced the invasiveness of cancer cells. Hence, we suggesting that these Cap-Au@MSNs can be used as promising candidates for cancer therapy and deserve further investigation.


Assuntos
Capsaicina/química , Raios Infravermelhos , Nanopartículas/química , Nanoestruturas/química , Dióxido de Silício/química , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Capsaicina/farmacologia , Capsaicina/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ouro/química , Humanos , Microscopia Confocal , Fotoquimioterapia , Porosidade , Câncer Papilífero da Tireoide/tratamento farmacológico , Câncer Papilífero da Tireoide/patologia
3.
Eur J Cancer Care (Engl) ; 28(5): e13120, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31184792

RESUMO

AIM: A randomised controlled trial (RCT) was implemented to verify the feasibility and acceptability of cognitive education in the format of mind maps for increasing perceived control and decreasing the symptom distress of lung cancer patients who were receiving chemotherapy. METHODS: A total of 136 lung cancer patients who were receiving chemotherapy were randomised using stratified blocks (1:1 ratio, from March 2016 to April 2017). The intervention group was given cognitive education in the format of mind maps. The control group was provided conventional education. The primary outcomes were perceived control, including cancer experience and cancer efficacy; the secondary outcomes included symptom distress (arising from fatigue, distress, sleep disturbance, poor appetite, drowsiness, shortness of breath, etc.). The Mann-Whitney U test, chi-squared test, two-sample t test and repeated measurement analysis of variance were used. RESULTS: Ninety-four patients completed the final study. The results of the repeated measurement analysis of variance indicated that at the 8th or 12th week following cognitive education intervention in the format of mind maps, the cancer experience, cancer efficacy (except personal efficacy) and symptom distress (arising from fatigue, distress, sleep disturbance, and sadness and its total scores) of the patients in the intervention group were considerably improved compared with those of the control group (p < 0.05). The longer the intervention was, the higher the level of the patients' perceived control was and the lower the degree of patient symptom distress was (p < 0.05). CONCLUSIONS: Our findings suggest that cognitive education in the format of mind maps could improve perceived control and decrease the symptom distress of lung cancer patients who were receiving chemotherapy and that it was feasible and acceptable. Cognitive education in the format of mind maps was found to be an effective teaching tool for lung cancer patients who were receiving chemotherapy.

4.
Cancer Med ; 8(10): 4782-4791, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31250987

RESUMO

PURPOSE: In the present study, we evaluated the expression and function of human long noncoding RNA (lncRNA) activated by DNA damage (NORAD) in human epithelial ovarian cancer (EOC). METHODS: NORAD expression was evaluated by qRT-PCR in EOC cell lines and in situ EOC clinical samples. Lentivirus-mediated NORAD downregulation was conducted in OVCAR-3 and ES-2 cells, and its effect on cancer cell proliferation, bufalin chemoresistance, cell-cycle transition in vitro, and xenotransplantation in vivo were examined, respectively. The likelihood of an lncRNA-microRNA (miRNA) signaling pathway was examined by probing the possible downstream competing target of NORAD, hsa-miR-155-5p. Moreover, hsa-miR-155-5p was knocked down in NORAD-downregulated EOC cells to functionally evaluate the correlation between NORAD and hsa-miR-155-5p in EOC. RESULTS: We found that NORAD was substantially upregulated in both EOC cell lines and human tumors. In OVCAR-3 and ES-2 cells, lentivirus-mediated NORAD downregulation had significant anticancer effects, as it suppressed cell proliferation, decreased bufalin chemoresistance, arrested cell-cycle transition, and inhibited xenograft growth. Also, hsa-miR-155-5p was confirmed to be the competing target of NORAD in EOC, and its knockdown in OVCAR-3 and ES-2 cells reversed the NORAD downregulation-induced anticancer functions. CONCLUSIONS: NORAD is upregulated in EOC. Inhibition of NORAD, possibly through endogenously competing against hsa-miR-155-5p, can be a new tumor-suppressing strategy in EOC.

5.
Biomed Pharmacother ; 115: 108891, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082772

RESUMO

Accumulating evidence has indicated the vital roles of long noncoding RNA (lncRNA) in the epithelial ovarian cancer (EOC). However, the function of lncRNA HAS2-AS1 in EOC is still unclear. This study aims to investigate the expression and role of HAS2-AS1 in EOC. In the cells and tissue of EOC, HAS2-AS1 expression was markedly up-regulated. Besides, the overexpression of HAS2-AS1 indicated the poor clinical outcome of EOC patients. Transcription factor CREB1 could bind with the promoter of HAS2-AS1 and activate its transcriptional expression. Functionally, HAS2-AS1 knockdown suppressed the proliferation, invasion and tumor growth of EOC cells in vitro and in vivo. Mechanical investigation found that HAS2-AS1 could relive the RUNX2 protein expression via sponging the miR-466, acting as miRNA sponge. In conclusion, this finding suggests the CREB1/HAS2-AS1/miR-466/RUNX2 axis in the in the EOC tumorigenesis, providing the novel insight for the molecular mechanism of EOC.


Assuntos
Proliferação de Células/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , MicroRNAs/metabolismo , Invasividade Neoplásica/fisiopatologia , Neoplasias Ovarianas/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Linhagem Celular Tumoral , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias Experimentais , RNA Longo não Codificante/genética , Organismos Livres de Patógenos Específicos , Transfecção
6.
Biomed Pharmacother ; 107: 1135-1141, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30257326

RESUMO

In this study, PEGylated selenium nanoparticles (PSNP) was successfully prepared and combined with X-ray for effective anticancer efficacy in lung cancer cells. The particles were nanosized and observed in spherical shape. The combination of PSNP and X-ray effectively killed the cancer cells and decreased the cell viability in a concentration dependent manner. PSNP combined with X-ray showed a significantly higher apoptosis of cancer cells with around 23% of cells in late apoptosis stage. Consistently, Caspase-3 activity was significantly higher when exposed to X-ray than in the absence of X-ray. The caspase-3 activity has been doubled in the presence of X-ray and PSNPs were actively involved in the activation of effector caspase-3 and downstream target. Importantly, treatment with the combination of PSNP and X-ray showed predominant red fluorescence which is indicative of dead cells. The results clearly indicate the cytotoxic potential of PSNP + X-ray combination against lung cancer cells. Overall, novel strategy of combination of PSNP and X-ray could be an alternative and effective chemo-radiotherapy.


Assuntos
Neoplasias Pulmonares/terapia , Nanopartículas , Polietilenoglicóis/química , Óxidos de Selênio/farmacologia , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quimiorradioterapia/métodos , Portadores de Fármacos/química , Humanos , Neoplasias Pulmonares/patologia , Óxidos de Selênio/administração & dosagem
7.
Cancer Gene Ther ; 25(11-12): 317-325, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29915283

RESUMO

The purpose of this work is to evaluate whether human microRNA-3129 (hsa-miR-3129) may functionally regulate cancer development, possibly through downstream target CD44 in human epithelial ovarian cancer (EOC). Direct targeting of hsa-miR-3129 on human CD44 transcript was evaluated using a dual-luciferase reporter assay. Gene expression of hsa-miR-3129 in immortal EOC cell lines was evaluated by qRT-PCR. Lentivirus-mediated hsa-miR-3129 upregulation or downregulation was conducted in SK-OV-3 and CAOV-3 cells, in which endogenous hsa-miR-3129 and CD44 expressions were then measured. In hsa-miR-3129 upregulated or downregulated EOC cells, functional assays were applied to evaluate EOC proliferation, bufalin chemoresistance in vitro, or xenotransplantation in vivo. Moreover, CD44 was ectopically overexposed in hsa-miR-3129 upregulated EOC cells to functionally evaluate the correlation between hsa-miR-3129 and CD44 in EOC. Dual-luciferase reporter assay confirmed hsa-miR-3129 directly binds CD44. QRT-PCR revealed that hsa-miR-3129 was substantially downregulated in EOC cell lines. In SK-OV-3 and CAOV-3 cells, lentivirus-induced hsa-miR-3129 upregulation downregulated CD44 whereas hsa-miR-3129 downregulation did not affect CD44 expression. Hsa-miR-3129 upregulation had significant anti-cancer effects by inhibiting EOC proliferation, increasing bufalin chemoresistance, and suppressing xenotransplantation. On the other hand, overexpressing CD44 reversed the anti-cancer functions by hsa-miR-3129 upregulation in EOC cells. In conclusion, Has-miR-3129 is a functional regulator, possibly through reverse targeting on CD44, in EOC.


Assuntos
Carcinoma Epitelial do Ovário/genética , Receptores de Hialuronatos/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Receptores de Hialuronatos/metabolismo , MicroRNAs/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Regulação para Cima
8.
J Exp Clin Cancer Res ; 35: 10, 2016 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-26762267

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs, which post-transcriptionally repress the expression of genes involved in cancer initiation and progression. Although some miRNAs that target many signaling pathways (also called universe miRNAs) are supposed to play a global role in diverse human tumors, their regulatory functions in gynecological cancers remain largely unknown. We investigated the biological role and underlying mechanism of miR-548c (one universe miRNA) in endometrial and ovarian cancer. METHODS: The effects of miR-548c overexpression on cell proliferation, migration and invasion were studied in endometrial and ovarian cancer cells. TWIST1 (Twist) was identified as a direct miR-548c target by western blot analysis and luciferase activity assay. The expression of miR-548c and Twist were examined by qRT-PCR in endometrial and ovarian cancer tissues. RESULTS: Here, we report that miR-548c is down-regulated in endometrial and ovarian cancer tissues when compared to normal tissues, and our meta-analysis reveal that decreased miR-548c expression correlates with poor prognosis in endometrial cancer patients. We show that in endometrial and ovarian cancer cells, ectopic expression of miR-548c significantly inhibits whereas knockdown of miR-548c dramatically induces cancer cell proliferation, migration and invasion. By using luciferase reporter assay, we demonstrate that Twist, a known oncogene in endometrial and ovarian cancers, is a direct target of miR-548c. Furthermore, the expression of Twist partially abrogates the tumor suppressive effects of miR-548c on cell migration and invasion. CONCLUSION: These findings suggest that miR-548c directly downregulates Twist, and provide a novel mechanism for Twist upregulation in both endometrial and ovarian cancers. The use of miR-548c may hold therapeutic potential for the treatment of Twist-overexpressing tumors.


Assuntos
Regulação para Baixo , Neoplasias do Endométrio/patologia , MicroRNAs/genética , Proteínas Nucleares/genética , Neoplasias Ovarianas/patologia , Proteína 1 Relacionada a Twist/genética , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Movimento Celular , Neoplasias do Endométrio/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Neoplasias Ovarianas/genética
10.
Artigo em Chinês | MEDLINE | ID: mdl-26540931

RESUMO

Approximately 3% of all head and neck neoplasms originate in the parotid gland and less than 1% are oncocytic. We present the rare case of a 63-year-old woman with oncocytic carcinoma of the parotid gland with facial nerve invasion and discuss the characteristics of this rare entity. Based on the results of medical history, physical examination, computed tomography and postoperative histopathological diagnosis, oncocytic carcinoma of the parotid gland was diagnosed. Treatment involved complete parotid gland removal and right neck dissection. Adjuvant radiotherapy and chemotherapy were followed by operation. As of 9 months following surgery, no recurrence has been identified, but long-term results are undefined.


Assuntos
Adenocarcinoma/patologia , Glândula Parótida/patologia , Neoplasias Parotídeas/patologia , Adenocarcinoma/terapia , Nervo Facial , Feminino , Humanos , Pessoa de Meia-Idade , Esvaziamento Cervical , Recidiva Local de Neoplasia , Neoplasias Parotídeas/terapia , Radioterapia Adjuvante , Tomografia Computadorizada por Raios X
11.
Sensors (Basel) ; 15(10): 25730-45, 2015 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-26473863

RESUMO

In this paper, the problem of non-rigid structure estimation in trajectory space from monocular vision is investigated. Similar to the Point Trajectory Approach (PTA), based on characteristic points' trajectories described by a predefined Discrete Cosine Transform (DCT) basis, the structure matrix was also calculated by using a factorization method. To further optimize the non-rigid structure estimation from monocular vision, the rank minimization problem about structure matrix is proposed to implement the non-rigid structure estimation by introducing the basic low-rank condition. Moreover, the Accelerated Proximal Gradient (APG) algorithm is proposed to solve the rank minimization problem, and the initial structure matrix calculated by the PTA method is optimized. The APG algorithm can converge to efficient solutions quickly and lessen the reconstruction error obviously. The reconstruction results of real image sequences indicate that the proposed approach runs reliably, and effectively improves the accuracy of non-rigid structure estimation from monocular vision.

12.
Biomed Res Int ; 2015: 974615, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25883982

RESUMO

Angiogenesis plays an important role in the progression of tumor. Besides being regulated by tumor cells per se, tumor angiogenesis is also influenced by stromal cells in tumor microenvironment (TME), for example, tumor associated macrophages (TAMs). Activating transcription factor 4 (ATF4), a member of the ATF/CREB family, has been reported to be related to tumor angiogenesis. In this study, we found that exogenous overexpression of ATF4 in mouse breast cancer cells promotes tumor growth via increasing tumor microvascular density. However, ATF4 overexpression failed to increase the expression level of a series of proangiogenic factors including vascular endothelial growth factor A (VEGFA) in tumor cells in this model. Thus, we further investigated the infiltration of proangiogenic macrophages in tumor tissues and found that ATF4-overexpressing tumors could recruit more macrophages via secretion of macrophage colony stimulating factor (M-CSF). Overall, we concluded that exogenous overexpression of ATF4 in breast cancer cells may facilitate the recruitment of macrophages into tumor tissues and promote tumor angiogenesis and tumor growth indirectly.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Macrófagos/metabolismo , Neoplasias Mamárias Experimentais/irrigação sanguínea , Neoplasias Mamárias Experimentais/metabolismo , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , Fator 4 Ativador da Transcrição/genética , Animais , Linhagem Celular Tumoral , Feminino , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/metabolismo , Macrófagos/patologia , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Neoplasias/genética , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Neuroreport ; 26(7): 429-37, 2015 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-25830493

RESUMO

Peripheral nerve functional recovery after injuries relies on both axon regeneration and remyelination. Both axon regeneration and remyelination require intimate interactions between regenerating neurons and their accompanying Schwann cells. Previous studies have shown that motor and sensory neurons are intrinsically different in their regeneration potentials. Moreover, denervated Schwann cells accompanying myelinated motor and sensory axons have distinct gene expression profiles for regeneration-associated growth factors. However, it is unknown whether differential motor and sensory functional recovery exists. If so, the particular one among axon regeneration and remyelination responsible for this difference remains unclear. Here, we aimed to establish an adult rat sciatic nerve crush model with the nonserrated microneedle holders and measured rat motor and sensory functions during regeneration. Furthermore, axon regeneration and remyelination was evaluated by morphometric analysis of electron microscopic images on the basis of nerve fiber classification. Our results showed that Aα fiber-mediated motor function was successfully recovered in both male and female rats. Aδ fiber-mediated sensory function was partially restored in male rats, but completely recovered in female littermates. For both male and female rats, the numbers of regenerated motor and sensory axons were quite comparable. However, remyelination was diverse among myelinated motor and sensory nerve fibers. In detail, Aß and Aδ fibers incompletely remyelinated in male, but not female rats, whereas Aα fibers fully remyelinated in both sexes. Our result indicated that differential motor and sensory functional recovery in male but not female adult rats is associated with remyelination rather than axon regeneration after sciatic nerve crush.


Assuntos
Axônios/fisiologia , Bainha de Mielina/fisiologia , Regeneração Nervosa/fisiologia , Recuperação de Função Fisiológica/fisiologia , Nervo Isquiático/lesões , Caracteres Sexuais , Envelhecimento , Animais , Axônios/ultraestrutura , Feminino , Masculino , Neurônios Motores/fisiologia , Neurônios Motores/ultraestrutura , Compressão Nervosa , Fibras Nervosas Mielinizadas/fisiologia , Ratos Sprague-Dawley , Nervo Isquiático/fisiopatologia , Nervo Isquiático/ultraestrutura , Células Receptoras Sensoriais/fisiologia , Células Receptoras Sensoriais/ultraestrutura , Tato/fisiologia , Caminhada/fisiologia
14.
Exp Ther Med ; 8(2): 347-354, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25009582

RESUMO

Previous studies have demonstrated the beneficial effect of graft-versus-tumor (GVT) following hematopoietic stem cell transplantation (HSCT) on the incidence of leukemia relapse and the overall survival rate of patients with leukemia; however, detailed mechanisms underlying the effects GVT exhibits on solid tumors following allogeneic HSCT are yet to be elucidated. The aim of the present study was to investigate the immune mechanism underlying the effect of interferon (IFN)-γ on GVT following allogeneic HSCT in breast cancer therapy. An in situ breast cancer mouse model was established by injecting 5×104 4T1 cells into the mammary fat pads of BALB/c mice. The 4T1 cells were transfected with the firefly luciferase reporter gene in order to monitor the tumor progression in real time. An allogeneic HSCT model was then established by transplanting bone marrow mononuclear cells from C57BL/6 mice to the BALB/c mice. To investigate the influence of T lymphocyte proliferation following allogeneic bone marrow transplantation, the levels of CD3+CD8+ cytotoxic T lymphocytes (CTLs) and CD4+CD25+ regulatory T cells were determined. In addition, IFN-γ and granzyme B expression levels in splenic lymphocytes were analyzed using flow cytometry. Allogeneic HSCT was found to significantly promote the proliferation and cytotoxicity of CTLs and suppress the growth of breast cancer. Furthermore, the secretory levels of IFN-γ and granzyme B by T cells were elevated following allogeneic HSCT. These results indicated that alloreactive T cells increased the secretion of IFN-γ, which promoted the alloresponse of donor CTLs. In addition, the CTLs produced granzyme B, which exerted a tumor suppressive effect.

15.
J Thorac Dis ; 6(5): 503-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24822110

RESUMO

ERBB2 mutations have been reported to occur in a subset of patients with lung adenocarcinomas or lung squamous cell carcinomas for some ethnicities, but it is unclear for Chinese patients with lung squamous cell carcinomas up to now. We retrospectively evaluated the status of ERBB2 mutations in a large cross-sectional cohort of 212 Chinese patients with non-small cell lung cancer (NSCLC) diagnosed in several hospitals from southern China during a time period of 1.5 years by polymerase chain reaction (PCR)-based direct sequencing and PCR-single strand conformation polymorphism (PCR-SSCP) analysis. ERBB2 mutation was found in 1 of 49 lung adenocarcinomas (2.0%) and none in lung squamous cell carcinomas and lung adenosquamous carcinomas. It implies the occurrence of ERBB2 mutations is infrequent in Chinese patients with NSCLC, especially in lung squamous cell carcinomas.

16.
J Nanosci Nanotechnol ; 14(5): 3305-12, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24734545

RESUMO

Polyamidoamine (PAMAM) dendrimers have been widely used as drug carriers, non-viral gene vectors and imaging agents. However, the use of dendrimers in biological system is constrained because of inherent toxicity and organ accumulation. In this study, the strategy of acetylation and PEGylation-acetylation was used to minimize PAMAM dendrimers toxicities and to improve their biodistribution and pharmacokinetics for medical application. PEGylated-acetylated PAMAM (G4-Ac-PEG) dendrimers were synthesized by PEGylation of acetylated PAMAM dendrimer of generation 4 (G4) with acetic anhydride and polyethylene glycol (PEG) 3.4 k. To investigate the cytotoxicity and in vivo biodistribution of the conjugates, in vitro cell viability analysis, Iodine-125 (125I) imaging, tissue distribution and hematoxylin-eosin (HE) staining were performed. We find that acetylation and PEGylation-acetylation essentially eliminates the inherent dendrimer cytotoxicity in vitro. Planar gamma (gamma) camera imaging revealed that all the conjugates were slowly eliminated from the body, and higher abdominal accumulation of acetylation PAMAM dendrimer was observed. Tissue distribution analysis showed that PEGylated-acetylated dendrimers have longer blood retention and lower accumulation in organs such as the kidney and liver than the non-PEGylated-acetylated dendrimers, but acetylation only can significantly increase the accumulation of G4 in the kidney and decrease the concentration in blood. Histology results reveal that no obvious damage was observed in all groups after high dose administration. This study indicates that PEGylation-acetylation could improve the blood retention, decrease organ accumulation, and improve pharmacokinetic profile, which suggests that PEGylation-acetylation provides an alternative method for PAMAM dendrimers modification.


Assuntos
Dendrímeros/síntese química , Dendrímeros/farmacocinética , Polietilenoglicóis/química , Acetilação , Animais , Dendrímeros/administração & dosagem , Células HEK293 , Humanos , Infusões Intravenosas , Radioisótopos do Iodo/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Tecidual
19.
World J Gastroenterol ; 19(29): 4791-8, 2013 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-23922479

RESUMO

AIM: To investigate stepwise sedation for elderly patients with mild/moderate chronic obstructive pulmonary disease (COPD) during upper gastrointestinal (GI) endoscopy. METHODS: Eighty-six elderly patients with mild/moderate COPD and 82 elderly patients without COPD scheduled for upper GI endoscopy were randomly assigned to receive one of the following two sedation methods: stepwise sedation involving three-stage administration of propofol combined with midazolam [COPD with stepwise sedation (group Cs), and non-COPD with stepwise sedation (group Ns)] or continuous sedation involving continuous administration of propofol combined with midazolam [COPD with continuous sedation (group Cc), and non-COPD with continuous sedation (group Nc)]. Saturation of peripheral oxygen (SpO2), blood pressure, and pulse rate were monitored, and patient discomfort, adverse events, drugs dosage, and recovery time were recorded. RESULTS: All endoscopies were completed successfully. The occurrences of hypoxemia in groups Cs, Cc, Ns, and Nc were 4 (9.3%), 12 (27.9%), 3 (7.3%), and 5 (12.2%), respectively. The occurrence of hypoxemia in group Cs was significantly lower than that in group Cc (P < 0.05). The average decreases in value of SpO2, systolic blood pressure, and diastolic blood pressure in group Cs were significantly lower than those in group Cc. Additionally, propofol dosage and overall rate of adverse events in group Cs were lower than those in group Cc. Finally, the recovery time in group Cs was significantly shorter than that in group Cc, and that in group Ns was significantly shorter than that in group Nc (P < 0.001). CONCLUSION: The stepwise sedation method is effective and safer than the continuous sedation method for elderly patients with mild/moderate COPD during upper GI endoscopy.


Assuntos
Endoscopia Gastrointestinal , Hipnóticos e Sedativos/administração & dosagem , Midazolam/administração & dosagem , Propofol/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Distribuição de Qui-Quadrado , China , Esquema de Medicação , Endoscopia Gastrointestinal/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Hipotensão/etiologia , Hipotensão/fisiopatologia , Hipóxia/sangue , Hipóxia/etiologia , Hipóxia/fisiopatologia , Masculino , Midazolam/efeitos adversos , Oxigênio/sangue , Propofol/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença
20.
Cell Transplant ; 22(11): 2079-90, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23067802

RESUMO

Endothelial progenitor cells (EPCs) have shown tropism towards primary tumors or metastases and are thus potential vehicles for targeting tumor therapy. However, the source of adult EPCs is limited, which highlights the need for a consistent and renewable source of endothelial cells for clinical applications. Here, we investigated the potential of human embryonic stem cell-derived endothelial cells (hESC-ECs) as cellular delivery vehicles for therapy of metastatic breast cancer. In order to provide an initial assessment of the therapeutic potency of hESC-ECs, we treated human breast cancer MDA-MB-231 cells with hESC-EC conditioned medium (EC-CM) in vitro. The results showed that hESC-ECs could suppress the Wnt/ß-catenin signaling pathway and thereby inhibit the proliferation and migration of MDA-MB-231 cells. To track and evaluate the possibility of hESC-EC-employed therapy, we employed the bioluminescence imaging (BLI) technology. To study the therapeutic potential of hESC-ECs, we established lung metastasis models by intravenous injection of MDA-MB-231 cells labeled with firefly luciferase (Fluc) and green fluorescent protein (GFP) to NOD/SCID mice. In mice with lung metastases, we injected hESC-ECs armed with herpes simplex virus truncated thymidine kinase (HSV-ttk) intravenously on days 11, 16, 21, and 26 after MDA-MB-231 cell injection. The NOD/SCID mice were subsequently treated with ganciclovir (GCV), and the growth status of tumor was monitored by Fluc imaging. We found that MDA-MB-231 tumors were significantly inhibited by intravenously injected hESC-ECs. The tumor-suppressive effects of the hESC-ECs, by inhibiting Wnt/ß-catenin signaling pathway and inducing tumor cell death through bystander effect in human metastatic breast cancer model, provide previously unexplored therapeutic modalities for cancer treatment.


Assuntos
Neoplasias da Mama/cirurgia , Células-Tronco Embrionárias/citologia , Células Endoteliais/citologia , Animais , Antivirais/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/transplante , Feminino , Ganciclovir/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Simplexvirus/genética , Timidina Quinase/genética
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