Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
1.
Cell Death Dis ; 15(8): 586, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138191

RESUMO

Anaplastic thyroid cancer (ATC) is among the most aggressive and metastatic malignancies, often resulting in fatal outcomes due to the lack of effective treatments. Prosapogenin A (PA), a bioactive compound prevalent in traditional Chinese herbs, has shown potential as an antineoplastic agent against various human tumors. However, its effects on ATC and the underlying mechanism remain unclear. Here, we demonstrate that PA exhibits significant anti-ATC activity both in vitro and in vivo by inducing GSDME-dependent pyroptosis in ATC cells. Mechanistically, PA promotes lysosomal membrane permeabilization (LMP), leading to the release of cathepsins that activate caspase 8/3 to cleave GSDME. Remarkably, PA significantly upregulates three key functional subunits of V-ATPase-ATP6V1A, ATP6V1B2, and ATP6V0C-resulting in lysosomal over-acidification. This over-acidification exacerbates LMP and subsequent lysosomal damage. Neutralization of lysosomal lumen acidification or inhibition/knockdown of these V-ATPase subunits attenuates PA-induced lysosomal damage, pyroptosis and growth inhibition of ATC cells, highlighting the critical role for lysosomal acidification and LMP in PA's anticancer effects. In summary, our findings uncover a novel link between PA and lysosomal damage-dependent pyroptosis in cancer cells. PA may act as a V-ATPase agonist targeting lysosomal acidification, presenting a new potential therapeutic option for ATC treatment.


Assuntos
Lisossomos , Piroptose , Carcinoma Anaplásico da Tireoide , ATPases Vacuolares Próton-Translocadoras , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Humanos , Piroptose/efeitos dos fármacos , ATPases Vacuolares Próton-Translocadoras/metabolismo , Carcinoma Anaplásico da Tireoide/metabolismo , Carcinoma Anaplásico da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Sapogeninas/farmacologia , Camundongos , Camundongos Nus , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Gasderminas
2.
Sci Rep ; 14(1): 14546, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914695

RESUMO

Caffeic acid phenethyl ester (CAPE) and its derivatives exhibit considerable effects against hepatocellular carcinoma (HCC), with unquestioned safety. Here we investigated CAPE derivative 1' (CAPE 1') monotherapy to HCC, compared with sorafenib. HCC Bel-7402 cells were treated with CAPE 1', the IC50 was detected using CCK-8 analysis, and acute toxicity testing (5 g/kg) was performed to evaluate safety. In vivo, tumor growth after CAPE 1' treatment was evaluated using an subcutaneous tumor xenograft model. Five groups were examined, with group 1 given vehicle solution, groups 2, 3, and 4 given CAPE 1' (20, 50, and 100 mg/kg/day, respectively), and group 5 given sorafenib (30 mg/kg/day). Tumor volume growth and tumor volume-to-weight ratio were calculated and statistically analyzed. An estimated IC50 was 5.6 µM. Acute toxicity tests revealed no animal death or visible adverse effects with dosage up to 5 g/kg. Compared to negative controls, CAPE 1' treatment led to significantly slower increases of tumor volume and tumor volume-to-weight. CAPE 1' and sorafenib exerted similar inhibitory effects on HCC tumors. CAPE 1' was non-inferior to sorafenib for HCC treatment, both in vitro and in vivo. It has great potential as a promising drug for HCC, based on effectiveness and safety profile.


Assuntos
Antineoplásicos , Ácidos Cafeicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Álcool Feniletílico , Sorafenibe , Ensaios Antitumorais Modelo de Xenoenxerto , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Animais , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Linhagem Celular Tumoral , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Camundongos Endogâmicos BALB C , Masculino
3.
J Cell Mol Med ; 26(12): 3527-3537, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35593216

RESUMO

Oxidative stress appears to play a role in the pathogenesis of diabetes mellitus erectile dysfunction (DMED). This study aimed to investigate the effect of N-acetylcysteine (NAC) on DMED in streptozotocin-induced diabetic mice and to explore potential mechanisms. In the present study, we show that an erectile dysfunction is present in the streptozotocin-induced mouse model of diabetes as indicated by decreases in intracavernous pressure responses to electro-stimulation as well as from results of the apomorphine test of erectile function. After treatment of NAC, the intracavernous pressure was increased. In these DMED mice, oxidative stress and inflammatory responses were significantly reduced within the cavernous microenvironment, while activity of antioxidant enzymes in this cavernous tissue was enhanced after NAC treatment. These changes protected mitochondrial stress damage and a significant decreased in apoptosis within the cavernous tissue of DMED mice. This appears to involve activation of the nuclear factor erythroid 2-like-2 (Nrf2) signalling pathway, as well as suppression of the mitogen-activated protein kinase (MAPK) p38/ NF-κB pathway within cavernous tissue. In conclusion, NAC can improve erectile function through inhibiting oxidative stress via activating Nrf2 pathways and reducing apoptosis in streptozotocin-induced diabetic mice. NAC might provide a promising therapeutic strategy for individuals with DMED.


Assuntos
Diabetes Mellitus Experimental , Disfunção Erétil , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Acetilcisteína/uso terapêutico , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Disfunção Erétil/complicações , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Estreptozocina/farmacologia
4.
Am J Transl Res ; 13(4): 3674-3681, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017550

RESUMO

OBJECTIVE: Care models of Healthcare Failure Mode and Effect Analysis (FMEA) were evaluated for the prevention of multi-drug resistant organisms (MDRO) infections in oral and maxillofacial surgery. METHODS: Two hundred patients who received oral and maxillofacial surgery from January to December 2017 were enrolled as the control group, and another 200 patients who received oral and maxillofacial surgery from January to December 2018 were enrolled as the FMEA group. The incidence of MDRO, the implementation of preventive and control measures, the mastery of preventive and control knowledge, and oral self-care ability were compared between the two groups. Risk Priority Number (RPN) and behavioral changes of health care personnel were observed in FMEA group. RESULTS: The FMEA group had a lower incidence of MDRO (2.00%) than the control group (6.00%) and a higher rate of acquisition of prevention and control knowledge (93.00%) than the control group (84.50%) (P < 0.05). Patients in FMEA group were higher than those in the control group in terms of compliance towards isolation signs and precautions, appropriate use of PPE, implementation of disinfection measures, hand hygiene and exercise of self-care agency (ESCA) scale scores (P < 0.05). The total RPN score of the FMEA group before and after management was 1384 and 180, respectively, and the reduction rate of total RPN scores was 86.99%. Scores with regard to knowledge, attitude, and behavior of health care personnel were increased after FMEA treatment (P < 0.05). CONCLUSION: The nursing model of FMEA for oral and maxillofacial surgery can prevent MDRO infections, reduce RPN, improve the implementation of preventive and control measures as well as oral self-care ability and the acquisition of knowledge.

5.
J Gene Med ; 23(7): e3344, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33885171

RESUMO

BACKGROUND: Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) acts as an oncogene in different cancers, although its roles in prostate cancer are not fully reported. We aimed to explore its mechanism in facilitating the malignancy of prostate cancer. METHODS: The expression of DANCR, microRNA (miR)-185-5p and LIM and SH3 protein 1 (LASP1) in 40 pairs of prostate cancer tissues and normal tissues, five prostate cancer cell lines and one epithelial cell line was assessed by a quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry, respectively. In transfected PC3 and C4-2 cells, cell proliferation, migration, invasion, cell cycle distribution and epithelial-mesenchymal transition (EMT) protein expression were tested via cell counting kit-8, wound healing, transwell, flow cytometry and western blot assays, respectively. The interactions between DANCR, miR-185-5p and LASP1 were verified by a dual-luciferase reporter assay. Rescue experiments were conducted to determine the roles of DANCR on the malignant properties of PC3 and C4-2 cells. The involvement of the signaling pathway was examined using a p-FAK inhibitor. RESULTS: DANCR and LASP1 expression was enhanced, whereas miR-185-5p expression was diminished in prostate cancer tissues and cell lines. Knockdown of DANCR suppressed cell proliferation, migration, invasion, G1-S transition and expression of EMT proteins of the transfected PC3 and C4-2 cells. DANCR sponged miR-185-5p to upregulate LASP1 expression. DANCR-miR-185-5p-LASP1 axis activates the FAK/PI3K/AKT/GSK3ß/Snail pathway to promote the malignant properties of PC3 and C4-2 cells. CONCLUSIONS: These findings suggest that DANCR exerts oncogenic roles in prostate cancer via the miR-185-5p/LASP1 axis activating the FAK/PI3K/AKT/GSK3ß/Snail pathway. It can be a potential biomarker in the diagnosis and monitoring of prostate cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas do Citoesqueleto/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas com Domínio LIM/metabolismo , MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Quinase 1 de Adesão Focal/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , MicroRNAs/genética , Células PC-3 , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais
6.
Front Physiol ; 12: 762847, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35069237

RESUMO

The interstitial cells in bladder lamina propria (LP-ICs) are believed to be involved in sensing/afferent signaling in bladder mucosa. Transient receptor potential (TRP) cation channels act as mechano- or chemo-sensors and may underlie some of the sensing function of bladder LP-ICs. We aimed to investigate the molecular and functional expression of TRP channels implicated in bladder sensory function and Piezo1/Piezo2 channels in cultured LP-ICs of the human bladder. Bladder tissues were obtained from patients undergoing cystectomy. LP-ICs were isolated and cultured, and used for real-time reverse transcription-quantitative polymerase chain reaction, immunocytochemistry, and calcium-imaging experiments. At the mRNA level, TRPA1, TRPV2, and Piezo1 were expressed most abundantly. Immunocytochemical staining showed protein expression of TRPA1, TRPV1, TRPV2, TRPV4, TRPM8, as well as Piezo1 and Piezo2. Calcium imaging using channel agonists/antagonists provided evidence for functional expression of TRPA1, TRPV2, TRPV4, Piezo1, but not of TRPV1 or TRPM8. Activation of these channels with their agonist resulted in release of adenosine triphosphate (ATP) from LP-ICs. Inhibition of TRPV2, TRPV4 and Piezo1 blocked the stretch induced intracellular Ca2+ increase. Whereas inhibition of TRPA1 blocked H2O2 evoked response in LP-ICs. Our results suggest LP-ICs of the bladder can perceive stretch or chemical stimuli via activation of TRPV2, TRPV4, Piezo1 and TRPA1 channels. LP-ICs may work together with urothelial cells for perception and transduction of mechanical or chemical signals in human-bladder mucosa.

7.
Open Med (Wars) ; 16(1): 58-67, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33364434

RESUMO

Bladder cancer is the most common malignant tumor of the urinary system. The intention of the present research is to explore the prognostic value and biological function of solute carrier family 12 member 8 (SLC12A8) in bladder cancer. The analysis based on the TCGA and ONCOMINE database revealed that the expression of SLC12A8 in bladder cancer was notably increased compared with the normal group. SLC12A8 expression was notably correlated with the age, pathological stage, T-stage, and lymph node metastasis of bladder cancer patients. Moreover, the patients' overall survival was notably shorter in the high SLC12A8 group. Compared with the control, SLC12A8 upregulation enhanced the proliferative, invasive, and migratory capacities of bladder cancer cells and promoted the expression of epithelial-mesenchymal transition (EMT) protein markers including ß-catenin, vimentin, snail, and slug, while reduced the expression of E-cadherin. In the case of downregulated SLC12A8 expression, the proliferative, invasive, and migratory capacities of bladder cancer cells and the expression of EMT protein markers presented the opposite trend. This study demonstrated that SLC12A8 was highly correlated with oncogenesis and progression of bladder cancer, indicating that SLC12A8 may be a meaningful biomarker for initial diagnosis and early treatment of bladder cancer.

8.
Female Pelvic Med Reconstr Surg ; 27(1): e180-e183, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33369967

RESUMO

OBJECTIVE: The objective of this study was to measure the anatomical distance from the cervicovaginal junction to the uterovesical peritoneal reflection (CJ-PR). METHODS: A total of 120 hysterectomy patients were selected as study subjects. The uterus was removed, and the CJ-PR distance was immediately measured. For total vaginal hysterectomy, measurement was performed intraoperatively. The cervical length was also measured postoperatively. RESULTS: The median (interquartile) CJ-PR distance for all subjects was 3.3 (2.9-3.7) cm. Comparison of premenopausal and postmenopausal women without prolapse revealed median CJ-PR distances of 3.3 (3.0-3.6) cm and 3.0 (2.6-3.4) cm, respectively. The CJ-PR distance was longer in women with prolapse (4.6 [3.7-5.6] cm) than in those without prolapse (3.2 [2.8-3.6] cm). The median cervical lengths were 3.1 (2.7-3.6) cm for postmenopausal patients without prolapse and 4.4 (3.6-5.8) cm for postmenopausal patients with prolapse. CONCLUSIONS: Knowledge of the CJ-PR distance may help gynecologists predict how far the uterovesical PR is from the anterior vaginal incision.


Assuntos
Colo do Útero/anatomia & histologia , Peritônio/anatomia & histologia , Bexiga Urinária/anatomia & histologia , Útero/anatomia & histologia , Vagina/anatomia & histologia , Adulto , Idoso , Pesos e Medidas Corporais , Feminino , Humanos , Histerectomia Vaginal , Pessoa de Meia-Idade
9.
Medicine (Baltimore) ; 99(47): e22998, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217801

RESUMO

It is necessary to identify the relationship between neck circumference and cardiovascular risk factors in patients with hypertension.Patients with hypertension treated in our hospital were included. The height, weight, neck circumference, waist circumference, fasting blood glucose, 2 h blood glucose (2hPPG), density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and glycated hemoglobin (HbA1c) were analyzed and compared.A total of 2860 patients with hypertension were included. There were significant differences between male and female patients in the neck circumference, waist circumference, fasting blood glucose, Total cholesterol, triacylglycerol, HDL-C, LDL-C, diabetes, metabolic syndrome, dyslipidemia, drinking and smoking (all P < .05); the neck circumference was positively correlated with waist circumference, body mass index (BMI), fasting blood glucose, 2hPPG, HbA1c, triacylglycerol and LDL-C (all P < .05), and negatively correlated with HDL-C (P = .014); as the neck circumference increases, the risk of hypertension, diabetes, metabolic syndrome, abdominal obesity, and dyslipidemia increases accordingly (all P < .05); the area under curve (AUC) was 0.827 and 0.812, and the neck circumference of 37.8 and 33.9 cm was the best cut-off point for male and female patients, respectively.Neck circumference is closely related to cardiovascular risk factors in patients with hypertension, which should be promoted in the screening of cardiovascular diseases.


Assuntos
Hipertensão/complicações , Pescoço/anatomia & histologia , Fatores Etários , Glicemia/análise , Estatura , Peso Corporal , Doenças Cardiovasculares/etiologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Circunferência da Cintura
10.
Sci Rep ; 9(1): 5659, 2019 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-30948734

RESUMO

A series of Ti/Li/Al ternary layered double hydroxides (TiLiAl-LDHs) with different Ti:Li:Al molar ratios were prepared by a coprecipitation method for photocatalytic CO2 reduction. It was demonstrated that the contents of anions between the layers of Ti/Li/Al-LDHs greatly determined the photocatalytic activity for CO2 reduction. With Ti:Li:Al molar ratios optimized to be 1:3:2, the largest contents of [Formula: see text]- anion and hydroxyl group were obtained for the Ti1Li3Al2-LDHs sample, which exhibited the highest photocatalytic activity for CO2 reduction, with CH4 production rate achieving 1.33 mmol h-1 g-1. Moreover, the theoretical calculations show that Ti1Li3Al2-LDHs is a p-type semiconductor with the narrowest band gap among all the obtained TiLiAl-LDHs. After calcined at high temperatures such as 700 °C, and the obtained TiLiAl-700 sample showed much increased photocatalytic activity for CO2 reduction, with CH4 production rate reaching about 1.59 mmol h-1 g-1. This calcination induced photocatalytic enhancement should be related to the cystal structure transformation from hydrotalcite to mixed oxides containing high reactive oxygen species for more efficient CO2 reduction.

11.
Stem Cell Res Ther ; 9(1): 159, 2018 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-29895333

RESUMO

BACKGROUND: Mesenchymal stem cells (MSC) have gained credibility as a therapeutic tool partly due to their potential to secrete factors such as cytokines and chemokines. Recently, exosomes, which mediate intercellular communication by delivering biomolecules such as mRNA and miRNA into recipient cells, have gained attention as a new and valuable therapeutic strategy in regenerative medicine. However, the potential role of exosomes secreted by adipose-derived mesenchymal stem cells (adMSC-Exos) in collagen metabolism is not well understood. The purpose of this study was to evaluate the effects of adMSC-Exos on collagen metabolism in cultured fibroblasts from women with stress urinary incontinence (SUI). METHODS: Periurethral vaginal wall tissues of postmenopausal women with or without SUI were collected during transvaginal surgical procedures. Primary fibroblasts were cultured from periurethral vaginal wall tissues, and the levels of type I collagen mRNA and protein were examined by qRT-PCR and western blotting. MSC were isolated from human adipose tissue by enzymatic digestion. Exosomes were prepared by ultracentrifugation of adMSC-conditioned medium (adMSC-CM) and were confirmed by transmission electron microscopy and western blot analyses. The effects of adMSC-CM and adMSC-Exos were assessed using qRT-PCR and western blotting. RESULTS: The type I collagen content was significantly decreased in periurethral vaginal wall tissues and cultured vaginal fibroblasts from women with SUI. adMSC-CM increased the expression of the col1a1 gene in vaginal fibroblasts from women with SUI. adMSC-Exos could be successfully isolated from adMSC-CM and could be transferred to fibroblasts efficiently. adMSC-Exos increased the expression of col1a1 in vaginal fibroblasts from women with SUI, and when the fibroblasts were treated with adMSC-Exos, the expression levels of TIMP-1 and TIMP-3 in fibroblasts were upregulated, with significant downregulation of MMP-1 and MMP-2 expression levels. CONCLUSIONS: adMSC-Exos increased type I collagen contents by increasing collagen synthesis and decreasing collagen degradation in vaginal fibroblasts from women with SUI. adMSC-Exos may be a novel therapeutic approach for treating SUI.


Assuntos
Colágeno Tipo I/metabolismo , Exossomos/metabolismo , Fibroblastos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Incontinência Urinária por Estresse/fisiopatologia , Feminino , Humanos
12.
Zhonghua Nan Ke Xue ; 23(4): 337-342, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29714419

RESUMO

OBJECTIVE: To compare three different pathways for transurethral seminal vesiculoscopy (SVS) and investigate the reliability and efficiency of transrectal ultrasonography (TRUS)-guided SVS (TRUS-SVS). METHODS: We retrospectively analyzed 90 cases of seminal vesiculoscopy conducted directly through the ejaculatory duct or prostatic utricle or under the guide of TRUS. We compared the success rate and complications among the three approaches. RESULTS: Operations were successfully performed in 87 (96.67%) of the 90 cases, 30 through the ejaculatory duct, 37 via the prostatic utricle, and 20 under the guide of TRUS, the operation time ranging from 25 to 75 minutes. Sperm was detected from the seminal vesicle fluid in (92.06%) of the azoospermia patients (58/63) during the surgery and in 77.78% of them (49/63) in semen analysis at 1 week postoperatively. Fifteen hematospermia and 12 spermatocystitis patients were cured. Postoperative follow-up found 20 cases of water-like semen and 3 cases of orchiepididymitis, but no such complications as retrograde ejaculation, incontinence, or rectourethral fistula. CONCLUSIONS: Transejaculatory duct and transprostatic utricle pathways are two common approaches to SVS, while TRUS-SVS may achieve a higher success rate and avoid injury of both the prostate and the rectum.


Assuntos
Glândulas Seminais/diagnóstico por imagem , Ultrassonografia/métodos , Azoospermia/diagnóstico por imagem , Ductos Ejaculatórios/diagnóstico por imagem , Epididimite/diagnóstico por imagem , Doenças dos Genitais Masculinos , Hemospermia/diagnóstico por imagem , Humanos , Masculino , Duração da Cirurgia , Próstata/diagnóstico por imagem , Reto , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sêmen , Análise do Sêmen , Espermatozoides , Ultrassonografia/estatística & dados numéricos
13.
Zhonghua Yi Xue Za Zhi ; 95(34): 2775-8, 2015 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-26711976

RESUMO

OBJECTIVE: To assess the feasibity and efficacy of narrow band imaging (NBI) cystoscopy assisted holmium laser resection of primary non-muscle invasive bladder cancer (HoLRBt). METHODS: During the period of May 2013 to December 2014, 150 cases of primary non-muscle invasive bladder cancer (NMIBC) admitted in our hospital were randomly divided into NBI-HoLRBt and WLI-TURBt group. In NBI-HoLRBt group, all suspicious lesion identified by either WLI or NBI were resected during the surgery with WLI and in NBI mode for lesion only visible with NBI. At the end of the procedure, NBI cystoscopic examination was performed again to identify whether there was residual lesions at the margins of the resection areas. In WLI-TURBt group, only WLI and TURBt were applied. All patients from the two groups underwent routine intravesical instillation after surgery. A total of 124 patients were diagnosed NMIBC by pathological findings (NBI-HoLRBt group: n=60, WLI-TURBt group: n=64), they were followed-up at 3 months, at which both WLI and NBI cystoscopy were performed to examine the residual tumor, and cytology was checked for all patients. The residual tumor rates at the first follow-up (RR-fFU) were recorded and compared. RESULTS: Baseline characteristics of the patient and the tumor were comparable between the two groups. The overall detection rate of NMIBC and carcinoma in situ (CIS) were significantly higher with NBI than WLI (94.5% (137/145) vs 75.8% (110/145), 16/17 vs 10/17, both P<0.05). The RR-fFU for NBI-HoLRBt and WLI-TURBt was 3.3% (2/60) and 17.2% (11/64), respectively (P<0.05). CONCLUSION: NBI-HoLRBt was feasible, and more effective for identification of NMIBC as well as for the reduction of residual tumor rate compared with WLI-TURBt.


Assuntos
Imagem de Banda Estreita , Neoplasias da Bexiga Urinária , Carcinoma in Situ , Cistoscopia , Hólmio , Humanos , Lasers de Estado Sólido , Invasividade Neoplásica , Neoplasia Residual
14.
Sci Rep ; 5: 14757, 2015 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-26437631

RESUMO

The liver resident lymphoid population is featured by the presence of a large number of CD3(+)CD56(+) cells referred as natural T cells. In human hepatocellular carcinoma (HCC) patients, the natural T cells were found to be sharply decreased in tumor (5.871 ± 3.553%) versus non-tumor (14.02 ± 6.151%) tissues. More intriguingly, a substantial fraction of the natural T cells (22.76 ± 18.61%) assumed FOXP3 expression. These FOXP3-expressing CD3(+)CD56(+) cells lost the expression of IFN-γ and perforin, which are critical for the effector function of natural T cells. On the other hand, they acquired surface expression of CD25 and CTLA-4 typically found in regulatory T (Treg) cells. Consistent with the phenotypic conversion, they imposed an inhibitory effect on anti-CD3-induced proliferation of naive T cells. Further studies demonstrated that transforming growth factor ß1 (TGF-ß1) could effectively induce FOXP3 expression in CD3(+)CD56(+) cells and the cells were thus endowed with a potent immunosuppressive capacity. Finally, Kaplan-Meier analysis revealed that the relative abundance of FOXP3-expressing CD3(+)CD56(+) cells in tumor tissues was significantly correlated with the survival of HCC patients. In conclusion, the present study identified a new type of regulatory immune cells whose emergence in liver cancer tissues may contribute to tumor progression.


Assuntos
Complexo CD3/imunologia , Antígeno CD56/imunologia , Carcinoma Hepatocelular/imunologia , Fatores de Transcrição Forkhead/imunologia , Neoplasias Hepáticas/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Complexo CD3/genética , Antígeno CD56/genética , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Linhagem da Célula/efeitos dos fármacos , Linhagem da Célula/imunologia , Reprogramação Celular/imunologia , Feminino , Citometria de Fluxo , Fatores de Transcrição Forkhead/genética , Expressão Gênica , Humanos , Imunofenotipagem , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/imunologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células , Análise de Sobrevida , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/patologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/patologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/imunologia , Fator de Crescimento Transformador beta1/farmacologia
15.
Zhonghua Yi Xue Za Zhi ; 95(37): 3032-5, 2015 Oct 06.
Artigo em Chinês | MEDLINE | ID: mdl-26814085

RESUMO

OBJECTIVE: To compare the differential effects of narrow band imaging (NBI)-assisted holmium laser with transurethral resection on the 1-year recurrence rate of non-muscle invasive bladder cancer (NMIBC), and to evaluate the clinical values of NBI-assisted holmium laser resection for NMIBC (NBI-HoLRBt). METHODS: During the period of February 2013 to February 2014, 178 cases of NMIBC were randomly divided into NBI-HoLRBt group and white light imaging (WLI) assisted transurethral resection of bladder tumor (WLI-TURBt) group. In NBI-HoLRBt, all suspicious lesion identified by either WLI or NBI were resected with WLI and in NBI mode for lesion only visible with NBI. At the end of the procedure, a NBI cystoscopic examination was performed to assess the margins of the resection areas and to identify eventual residual lesions. In WLI-TURBt group, only WLI and TURBt were applied. All patients underwent routine follow-up with WLI and NBI cystoscopy supplemented with cytology every 3 month. The recurrence risk of patients with NMIBC subjected to either NBI-HoLRBt or WLI-TURBt was compared at 3 and 12 month. RESULTS: The 3-month and 1-year recurrence rate was 18.48% (17/92) and 38.04% (35/92) respectively in the WLI-TURBt group, it was 5.81% (5/86) and 18.60% (16/86) in the NBI-HoLRBt group (both P<0.05). In addition, the in situ recurrence rate was less in the NBI-HoLRBt than WLI-TURBt group (2.33% vs 14.13%, P<0.05). CONCLUSION: NBI-assisted holmium laser resection of bladder tumor can reduce the 3-month and 1-year recurrence risk of NMIBC and should be considered a valuable clinical therapeutic method for NMIBC.


Assuntos
Imagem de Banda Estreita , Neoplasias da Bexiga Urinária , Cistoscopia , Hólmio , Humanos , Lasers de Estado Sólido , Luz , Recidiva Local de Neoplasia , Estudos Prospectivos
16.
Oncol Rep ; 30(3): 1157-64, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23799592

RESUMO

Recent studies have indicated that telomerase activity promotes cancer invasion and metastasis, but the underlying mechanism remains unclear. Several studies have shown that expression of exogenous human telomerase reverse transcriptase (hTERT) can promote motility and invasiveness among telomerase-negative tumor cells, and inhibition of endogenous telomerase activity can reduce invasiveness in tumor cells. However, whether overexpression of hTERT can further enhance the motility and invasiveness of telomerase­positive tumor cells has yet to be determined. In the present study, we showed that stable overexpression of hTERT can increase telomerase activity and telomere length, which significantly promotes the invasive and metastatic potential of telomerase­positive HepG2 cells but does not affect cell proliferation. Further analysis suggested that enhanced invasiveness and metastasis may act through corresponding upregulation of mRNA and protein expression of matrix metalloproteinase 9 (MMP9) and Ras homolog gene family member C (RhoC). Our study indicated that exogenous expression of hTERT may promote invasiveness and metastasis through upregulation of MMP9 and RhoC.


Assuntos
Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Telomerase/metabolismo , Western Blotting , Vetores Genéticos , Células Hep G2 , Humanos , Técnicas In Vitro , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Invasividade Neoplásica , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Retroviridae/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Telomerase/genética , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Proteína de Ligação a GTP rhoC
17.
Biochem Biophys Res Commun ; 411(3): 530-5, 2011 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-21756876

RESUMO

Therapeutic numbers of antigen-specific cytotoxic T lymphocytes (CTLs) are key effectors in successful adoptive immunotherapy. However, efficient and reproducible methods to meet the qualification remain poor. To address this issue, we designed the artificial antigen-presenting cell (aAPC) system based on poly(lactic-co-glycolic acid) (PLGA). A modified emulsion method was used for the preparation of PLGA particles encapsulating interleukin-2 (IL-2). Biotinylated molecular ligands for recognition and co-stimulation of T cells were attached to the particle surface through the binding of avidin-biotin. These formed the aAPC system. The function of aAPCs in the proliferation of specific CTLs against human Flu antigen was detected by enzyme-linked immunospot assay (ELISPOT) and MTT staining methods. Finally, we successfully prepared this suitable aAPC system. The results show that IL-2 is released from aAPCs in a sustained manner over 30 days. This dramatically improves the stimulatory capacity of this system as compared to the effect of exogenous addition of cytokine. In addition, our aAPCs promote the proliferation of Flu antigen-specific CTLs more effectively than the autologous cellular APCs. Here, this aAPC platform is proved to be suitable for expansion of human antigen-specific T cells.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Células Artificiais/imunologia , Imunoterapia Adotiva , Fragmentos de Peptídeos/imunologia , Linfócitos T Citotóxicos/imunologia , Proteínas da Matriz Viral/imunologia , Avidina/química , Biotina/química , Biotinilação , Cápsulas , ELISPOT , Humanos , Interleucina-2/química , Interleucina-2/imunologia , Ácido Láctico/química , Ligantes , Ativação Linfocitária , Microesferas , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Linfócitos T Citotóxicos/transplante
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA