Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
3.
Medicine (Baltimore) ; 99(1): e18575, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895803

RESUMO

This was a meta-analysis of epidemiological articles that aimed to estimate the association of garlic intake with the risk of colorectal cancer (CRC).Electronic databases, including the Cochrane Database of Systematic Reviews, PubMed, and EMBASE, were systemically searched from inception to May 2019 to identify related articles. In addition, a random model was used to pool the included evidence based on heterogeneity. Additionally, subgroup analyses were carried out to examine the differences between different groups. The stability of our findings was tested through sensitivity analyses. Publication bias was also assessed by Egger and Begg tests. Moreover, all enrolled studies were ordered according to the publication year for a cumulative meta-analysis.A total of 11 studies (involving 12,558 cases) were included in the current meta-analysis. Our integrated relative risk (RR) of CRC was 0.80 (95% confidence interval [CI], 0.69-0.91) for the highest versus the lowest garlic consumption categories (RR: 0.71 [95% CI, 0.60-0.84] for controls and RR: 0.99 [95% CI, 0.80-1.23] for cohorts). There was significant heterogeneity across all enrolled studies (I = 68.3%, P < .01). The sensitivity analysis revealed no notable alterations of the integrated results. According to the funnel plot regarding garlic intake and the risk of CRC, together with the Egger test (P = .1) and Begg test (P = .064) results, there was no notable evidence of publication bias. The cumulative meta-analysis suggested that the 95% CIs became narrower with the increase in sample size.Based on the existing evidence, garlic intake could reduce the risk of CRC.


Assuntos
Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Alho , Adulto , Idoso , Ingestão de Alimentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
4.
Cancer Biol Ther ; 20(9): 1187-1194, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31018748

RESUMO

Objective: To explore a method for culturing hepatocellular carcinoma and tumor-infiltrating lymphocytes (HCC-TIL) and investigate the mechanism of TIL in killing tumors. Methods: The distribution of regulatory T cells (Treg) in HCC was detected by immunohistochemistry. Conventional TIL and oligoclonal TIL were isolated by the traditional method of enzyme digestion combined with mechanical treatment for whole HCC and micro HCC tissue block culturing method. MTT was used to compare the killing activity of TIL. Flow cytometry was used to analyze the proportion of CD8+ T cells and Treg cells in TIL. Tumor-bearing mice were established, and TIL adoptive immunotherapy was performed. Results: Treg cells were mainly distributed in the stroma of HCC. In vitro experiments showed oligoclonal TIL had higher cytotoxicity to tumor cells which negatively correlated with the proportion of Treg cells. In vivo experiments showed oligoclonal TIL had a higher anti-tumor effect. IFN-γ in peripheral blood and the positive rate of intratumoral lymphocytic infiltration in oligoclonal TIL group were both higher. TGF-ß and IL-10 in peripheral blood and the positive rate of intratumoral FoxP3 and IL-17 were both lower than those in conventional TIL group. Conclusion: The oligoclonal TIL culture method could obtain TIL with higher purity, and cytotoxicity to tumor cells was associated with Treg cells. The oligoclonal TIL had cytotoxicity to autologous HCC cells and significant inhibitory effect on the growth of transplanted tumors. The mechanism might be associated with the inhibition of Treg cells proliferation, increase of IFN-γ secretion, and decrease of TGF-ß, IL-10, and IL-17 secretion.

5.
Aging (Albany NY) ; 10(12): 4084-4092, 2018 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-30563955

RESUMO

Interleukin (IL)-1B reportedly promotes the stemness and invasiveness of colon cancer cells. Several studies have investigated the association between IL-1B gene polymorphisms and colorectal cancer (CRC) risk, but report conflicting findings. Here, this association was explored in a hospital-based case-control study involving 527 CRC cases and 639 controls from two Chinese Han populations. Genotyping was done by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The IL-1B expression in CRC patients and controls were obtained from the GEPIA database and the mRNA expressions of different genotypes were downloaded from the GTEx portal database. The relationship of two IL-1B gene loci with clinical parameters and overall survival were analyzed using the Chi-square test and Kaplan-Meier analysis with the log-rank test respectively. It was found that the IL-1B mRNA levels in CRC patients were significantly higher than in controls. Bioinformatic analysis suggested that rs1143634 and rs1143623 polymorphisms decreased the IL-1B mRNA expression. The two polymorphisms were associated with decreased risk for CRC. Stratified analyses revealed the IL-1B gene rs1143623 and rs1143634 polymorphisms decreased the risk of CRC among females, smokers and drinkers. Moreover, the CC and/or GC genotype of rs1143623 polymorphism were correlated with decreased risk among CRC patients with tumor size ≥5cm, TNM stage III+IV, and rectal cancer. For rs1143634 polymorphism, the CT genotype reduced the risk of colorectal adenocarcinoma. The CRC patients carrying CC genotype of rs1143623 polymorphism were associated with better overall survival. In conclusion, IL-1B gene rs1143623 and rs1143634 polymorphisms are associated with decreased risk for CRC patients and thereby play important roles in the etiology of CRC.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Interleucina-1beta/genética , Polimorfismo Genético , Idoso , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Bases de Dados Genéticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
Zhongguo Yi Liao Qi Xie Za Zhi ; 42(6): 464-465, 2018 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-30560633

RESUMO

OBJECTIVE: To explore the application value of rectal prolapse constipation balloon in single auxiliary defecation. METHODS: Forty-one patients with moderate or severe rectocele were treated with a rectocele constipation balloon through the vagina. The defecography and VAS scores were compared before and after implantation. RESULTS: There was a significant difference between the anorectal angle, rectocele, and VAS scores before and after intervention in defecography (P<0.01). CONCLUSIONS: A single assisted defecation of the rectocelicular constipation balloon is feasible.


Assuntos
Defecação , Defecografia , Prolapso Retal , Constipação Intestinal/diagnóstico , Defecografia/instrumentação , Feminino , Humanos , Retocele
7.
Cancer Lett ; 425: 54-64, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29608986

RESUMO

Hepatocellular carcinoma (HCC) is the second leading cause of cancer related death which needs novel drugs to improve patient outcome. Survivin overexpresses in HCC and contributes to HCC malignant progression. In this study, we established a Survivin-targeted drug screening platform, a cell model HepG2-Sur5P-EGFP-Sur3U stably transfected with lentivirus carrying an EGFP expression cassette, in which the EGFP expression was regulated by the upstream Survivin promoter and downstream Survivin 3'-UTR. By using this platform, we screened and easily identified one of matrine derivatives, WM-127, from hundreds of matrine derivatives. WM-127 was demonstrated to be a strong Survivin inhibitor that inhibited cell proliferation, induced cell cycle arrest and apoptosis of HCC cells, and suppressed the growth of HCC xenografted tumors in nude mice, suggesting that WM-127 might be a promising drug for HCC treatment. WM-127 exhibited less cytotoxicity in normal cells. Mechanistic studies showed that WM-127 suppressed the activity of Survivin/ß-catenin pathway and the expression of Bax to induce cell cycle arrest and apoptosis. Taken together, we constructed an economical, practical, efficient and convenient cell platform for screening the Survivin-targeted drugs from the enormous diversity of chemicals or factors, which would be a potential tool for antitumor drug research and development.


Assuntos
Alcaloides/administração & dosagem , Alcaloides/síntese química , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Survivina/antagonistas & inibidores , Alcaloides/química , Alcaloides/farmacologia , Animais , Carcinoma Hepatocelular/metabolismo , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Nus , Via de Sinalização Wnt/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Genes Cells ; 23(1): 35-45, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29210217

RESUMO

CD147 is highly expressed in hepatocellular carcinoma (HCC) and associated with the invasion and metastasis of HCC. The efficacy of I131 -metuximab (I131 -mab), a newly developed agent that targets CD147, as a radio-immunotherapy for local HCC, has been validated in clinical practice. However, the synergistic anticancer activity and molecular mechanism of different conjugated components within I131 -mab remain unclear. In this study, the cytological experiments proved that I131 -mab inhibited the proliferation and invasion of HCC cells. Mechanically, this inhibition effect was mainly mediated by the antibody component part of I131 -mab, which could reverse the epithelial-mesenchymal transition of HCC cells partially by suppressing the phosphorylation of VEGFR-2. The inhibitory effect of I131 on HCC cell proliferation and invasion is limited, whereas, when combined with metuximab, I131 significantly enhanced the sensitivity of HCC cells to CD147-mab and consequently reinforced the anticancer effects of CD147-mab, suggesting that the two components of I131 -mab exerted synergistic anti-HCC capability. Furthermore, the experiments using SMMC-7721 human HCC xenografts in athymic nude mice showed that I131 -mab and CD147-mab significantly inhibited the growth of xenograft tumors and that I131 -mab was more effective than CD147-mab. In conclusion, our results elucidated the mechanism underlying the anti-HCC effects of I131 -mab and provided a theoretical foundation for the clinical application of I131 -mab.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação , Células Tumorais Cultivadas , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Oncotarget ; 8(20): 32523-32535, 2017 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-28430645

RESUMO

Midkine is overexpressed in hepatocellular carcinoma (HCC) and plays a role in tumor progression, but less is known about its role in resistance of circulating tumor cells (CTCs) to anoikis which leading to recurrence and metastasis. The aim of the present study was to analyze whether midkine was associated with HCC progression with anoikis resistance. We found that cultured HCC cells were more resistant to anoikis, which paralleled midkine expression, and midkine treatment significantly inhibited anoikis in a dose-dependent manner. Furthermore, in in vitro and in vivo assays, knockdown of midkine resulted in significant sensitivity to anoikis, decreased cell survival and significantly decreased tumor occurrence rate. Patients with midkine-elevated HCC had higher CTC counts and less apoptotic CTCs, as well as significantly higher recurrence rate and shorter recurrence-free interval. To understand the molecular mechanism underlying the midkine with HCC progression, we performed in vitro and in vivo studies. We found that midkine plays an important role in enhancement of HCC cell resistance to anoikis, thereby promoting subsequent metastasis. Activation of PI3K/Akt/NF-κB/TrkB signaling by midkine-activated anaplastic lymphomakinase (ALK) is responsible for anoikis resistance.


Assuntos
Anoikis/genética , Carcinoma Hepatocelular/genética , Citocinas/metabolismo , Neoplasias Hepáticas/genética , Animais , Carcinoma Hepatocelular/patologia , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Midkina , Metástase Neoplásica , Células Neoplásicas Circulantes/patologia
10.
Zhen Ci Yan Jiu ; 42(6): 533-6, 2017 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-29318862

RESUMO

OBJECTIVE: To evaluate the effect on postoperative complications of mixed hemorrhoids treated with electroacupuncture(EA) at Chengshan(BL 57),Dachangshu(BL 25)and Erbai(EX-UE 2). METHODS: A total of 60 patients with mixed hemorrhoids were randomly divided into control and EA groups,30 cases in each group. In addition to basic treatment, EA was applied at BL 57, BL 25 and EX-UE 2 for 30 min (2 Hz/15 Hz,0.5-2 mA) each day for 3 days after surgery in the EA group, while the control group received basic treatment after surgery. Postoperative complications after treatment were evaluated each day. RESULTS: Following surgery, anal pain, anal pendant expansion and hematochezia were observed in both the EA group and control group. On the first day after surgery, symptom improvement was not statistically significantly different between the two groups (P>0.05).On the 2nd and 3rd days after surgery, anal pain, anal pendant expansion and hematochezia were markedly improved in the EA group compared with those in the control group (P<0.05). CONCLUSIONS: Electroacupuncture can reduce anal pain, anal pendant expansion and hematochezia after surgery in patients with mixed hemorrhoids.


Assuntos
Eletroacupuntura , Hemorroidas , Pontos de Acupuntura , Eletroacupuntura/efeitos adversos , Humanos , Complicações Pós-Operatórias
11.
Artigo em Inglês | MEDLINE | ID: mdl-29445412

RESUMO

Traditional Chinese medicine was reported to have good effects in treating functional constipation. This work attempted to prove the effects of aqueous extracts of Herba Cistanche (AEHC) on STC treatment and to determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. HPLC was performed for identification and confirmation of the bioactive components in the AEHC. It was found that AEHC attenuated STC responses based on increased fecal quantity, moisture content, and intestinal transit rate, as well as serum levels of GAS, MTL, SS, and CGRP. The protein and mRNA levels of c-kit, a labeling of interstitial cells of Cajal (ICC), also increased. Meanwhile, only the protein level of SCF, a ligand of c-kit, increased. The analysis of our data suggested that AEHC could obviously improve the function of ICC via a signaling pathway involving PI3K, SCF, and c-kit and enhance colonic motility indices such as GAS, MTL, SS, and CGRP. It is interesting to note that AEHC appeared to be effective on constipation, so further experiments are necessary to clarify the exact mechanisms involved.

12.
Oncotarget ; 7(31): 49143-49155, 2016 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-27172795

RESUMO

In diffuse large B-cell lymphoma (DLBCL), many oncogenic microRNAs (OncomiRs) are highly expressed to promote disease development and progression by inhibiting the expression and function of certain tumor suppressor genes, and these OncomiRs comprise a promising new class of molecular targets for the treatment of DLBCL. However, most current therapeutic studies have focused on a single miRNA, with limited treatment outcomes. In this study, we generated tandem sequences of 10 copies of the complementary binding sequences to 13 OncomiRs and synthesized an interfering long non-coding RNA (i-lncRNA). The highly-expressed i-lncRNA in DLBCL cells would compete with the corresponding mRNAs of OncomiR target genes for binding OncomiRs, thereby effectively consuming a large amount of OncomiRs and protecting many tumor suppressor genes. The in vitro experiments confirmed that the i-lncRNA expression significantly inhibited cell proliferation, induced cell cycle arrest and apoptosis in DLBCL cell lines, mainly through upregulating the expression of PTEN, p27kip1, TIMP3, RECK and downregulating the expression of p38/MAPK, survivin, CDK4, c-myc. In the established SUDHL-4 xenografts in nude mice, the treatment strategy involving adenovirus-mediated i-lncRNA expression significantly inhibited the growth of DLBCL xenografts. Therefore, this treatment would specifically target the carcinogenic effects of many OncomiRs that are usually expressed in DLBCL and not in normal cells, such a strategy could improve anti-tumor efficacy and safety and may be a good prospect for clinical applications.


Assuntos
Linfoma Difuso de Grandes Células B/terapia , MicroRNAs/antagonistas & inibidores , RNA Longo não Codificante/genética , Animais , Apoptose , Carcinogênese/genética , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Fluorescência Verde/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Transplante de Neoplasias , Oncogenes , Ligação Proteica
13.
Tumour Biol ; 37(6): 8047-55, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26711788

RESUMO

Sorafenib is a multikinase inhibitor for the treatment of hepatocellular carcinoma. However, most patients who initially respond to sorafenib become refractory. In a previous study, we demonstrated that sphere-forming cells derived from liver cancer cell lines possess the properties of liver cancer stem cells (LCSCs). In the present study, we found that successive passages of LCSCs were more resistant to sorafenib, and LCSCs treated with sorafenib showed an increase in spheroid formation with a lower inhibition rate. MK2206, but not various other inhibitors of cell signaling pathways, enhanced their sensitivity to sorafenib, increased the apoptotic rate, and suppressed the growth of LCSC xenografts in vivo (P < 0.01); sorafenib treatment decreased the level of active phosphorylated (p)Akt (Thr308) and reduced the levels of active pAkt (Ser473) and extracellular signal-regulated kinase (ERK) in LCSCs, whereas MK2206 reduced pAkt expression and increased pERK expression. Cotreatment with sorafenib and MK2206 reduced pAkt and pERK expression in LCSCs and xenografted tumors (P < 0.01). Treatment with either sorafenib or MK2206 decreased the expression of EpCAM and CD133 in LCSCs, which was more evident after combined treatment. Based on these results, we conclude that resistance to sorafenib is associated with weak ERK signaling and strong Akt signaling in LCSCs. By inhibition of Akt and upregulation of ERK, MK2206 overcomes the resistance of LCSCs to sorafenib.


Assuntos
Carcinoma Hepatocelular/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Células-Tronco Neoplásicas/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Niacinamida/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sorafenibe , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Oncotarget ; 7(3): 2646-59, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26544731

RESUMO

Sorafenib is a multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC). However, therapeutic response to sorafenib was not equal among HCC patients. Here we present a novel system to provide quantitative information concerning sorafenib-related targets by simultaneous detection of phosphorylated ERK (pERK) and pAkt expressions in circulating tumor cells (CTCs) isolated from HCC patients. Our results showed that 90.0% of patients had a molecular classification of tissues concordant with that of CTCs. CTC counts showed a shaper decline in patients with pERK+/pAkt- CTCs after two weeks of sorafenib treatment (P < 0.01). Disease control rates were significantly different between patients with pERK+/pAkt- CTCs (11/15; 73.3%) and those without (13/44; 29.5%) (P < 0.05). Univariate and multivariate analysis indicated pERK+/pAkt- CTCs as an independent predictive factor of progression-free survival (PFS) (hazard ratio = 9.389; P < 0.01). PFS correlated with the proportion of pERK+/pAkt- CTCs (r = 0.968, P < 0.01), and was higher in patients with ≥ 40% pERK+/pAkt- CTCs compared to those with < 40% (8.4 vs. 1.3 mo; P < 0.05). In a validation set of twenty HCC patients, CTCs from patients with ≥ 40% pERK+/pAkt- CTCs had significantly higher inhibition rates of spheroid formation compared to those with < 40% (61.2 vs. 19.8%; P < 0.01). Our findings demonstrated that CTCs can be used in place of tumor tissue for characterization of pERK/pAkt expression. pERK+/pAkt- CTCs are most sensitive to sorafenib and an independent predictive factor of PFS in HCC patients treated with sorafenib.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes/patologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Proliferação de Células/efeitos dos fármacos , Feminino , Imunofluorescência , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Células Neoplásicas Circulantes/efeitos dos fármacos , Niacinamida/farmacologia , Fosforilação/efeitos dos fármacos , Prognóstico , Sorafenibe , Taxa de Sobrevida , Células Tumorais Cultivadas
15.
World J Gastroenterol ; 21(10): 2918-25, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25780289

RESUMO

AIM: To improve an asialoglycoprotein receptor (ASGPR)-based enrichment method for detection of circulating tumor cells (CTCs) of hepatocellular carcinoma (HCC). METHODS: Peripheral blood samples were collected from healthy subjects, patients with HCC or various other cancers, and patients with hepatic lesions or hepatitis. CTCs were enriched from whole blood by extracting CD45-expressing leukocytes with monoclonal antibody coated-beads following density gradient centrifugation. The remaining cells were cytocentrifuged on polylysine-coated slides. Isolated cells were treated by triple immunofluorescence staining with CD45 antibody and a combination of antibodies against ASGPR and carbamoyl phosphate synthetase 1 (CPS1), used as liver-specific markers, and costained with DAPI. The cell slide was imaged and stained tumor cells that met preset criteria were counted. Recovery, sensitivity and specificity of the detection methods were determined and compared by spiking experiments with various types of cultured human tumor cell lines. Expression of ASGPR and CPS1 in cultured tumor cells and tumor tissue specimens was analyzed by flow cytometry and triple immunofluorescence staining, respectively. RESULTS: CD45 depletion of leukocytes resulted in a significantly greater recovery of multiple amounts of spiked HCC cells than the ASGPR(+) selection (Ps < 0.05). The expression rates of either ASGPR or CPS1 were different in various liver cancer cell lines, ranging between 18% and 99% for ASGPR and between 9% and 98% for CPS1. In both human HCC tissues and liver cancer cell lines, there were a few HCC cells that did not stain positive for ASGPR or CPS1. The mixture of monoclonal antibodies against ASGPR and CPS1 identified more HCC cells than either antibody alone. However, these antibodies did not detect any tumor cells in blood samples spiked with the human breast cancer cell line MCF-7 and the human renal cancer cell line A498. ASGPR(+) or/and CPS1(+) CTCs were detected in 29/32 (91%) patients with HCC, but not in patients with any other kind of cancer or any of the other test subjects. Furthermore, the improved method detected a higher CTC count in all patients examined than did the previous method (P = 0.001), and consistently achieved 12%-21% higher sensitivity of CTC detection in all seven HCC patients with more than 40 CTCs. CONCLUSION: Negative depletion enrichment combined with identification using a mixture of antibodies against ASGPR and CPS1 improves sensitivity and specificity for detecting circulating HCC cells.


Assuntos
Receptor de Asialoglicoproteína/sangue , Biomarcadores Tumorais/sangue , Carbamoil-Fosfato Sintase (Amônia)/sangue , Carcinoma Hepatocelular/sangue , Separação Celular/métodos , Citometria de Fluxo , Neoplasias Hepáticas/sangue , Células Neoplásicas Circulantes/metabolismo , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Feminino , Imunofluorescência , Células Hep G2 , Humanos , Antígenos Comuns de Leucócito/sangue , Neoplasias Hepáticas/patologia , Células MCF-7 , Masculino , Células Neoplásicas Circulantes/patologia , Reprodutibilidade dos Testes
16.
Clin Chim Acta ; 451(Pt B): 208-14, 2015 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-25661085

RESUMO

BACKGROUND: Observational studies on the prognostic role of thyroid transcription factor 1 (TTF-1) in non-small-cell lung cancer (NSCLC) are controversial. METHODS: To clarify the impact of TTF-1 in NSCLC survival, we performed this meta-analysis that included eligible studies. The combined hazard ratios and their corresponding 95% confidence intervals were calculated in terms of overall survival. RESULTS: A total of 17 studies with 2235 patients were evaluable for this meta-analysis. The studies were categorized by histology, disease stage and patient race. Our results suggested that TTF-1 overexpression had a favorable impact on survival of patients with NSCLC, the HR (95% CI) was 0.49 (0.42 to 0.55) overall, 0.46 (0.38-0.54) in Asian patients, 0.52 (0.42-0.63) in non-Asian patients, 0.45 (0.38-0.52) in adenocarcinoma, 0.63 (0.39-0.86) in stage I NSCLC, and 0.43 (0.33-0.53) in stage IIIb-IV NSCLC. The data collected were not sufficient to determine the prognostic value of VEGF in patients with squamous cell lung carcinomas. But there was a high heterogeneity between the studies. CONCLUSION: TTF-1 overexpression indicates a favorable prognosis for patients with NSCLC, this effect appears also significant when the analysis is restricted in lung AC patients, stage I and stage IIIb-IV NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Ligação a DNA/biossíntese , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Humanos , Prognóstico , Análise de Sobrevida , Fatores de Transcrição
17.
Cancer Lett ; 361(1): 22-32, 2015 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-25687885

RESUMO

Anoikis is a form of apoptosis which occurs when anchorage-dependent cells either show loss of adhesion or inappropriate adhesion. Only a few cancer cells that detach from the primary site of the tumor acquire the ability to resist anoikis and form metastasis. The mechanism underlying the resistance of colorectal cancer (CRC) cells to anoikis remains unclear. Interleukin-8 (alternatively known as CXCL8) is associated with CRC angiogenesis and progression. Here, we found that a high abundance of CXCL8 or TOPK strongly correlated with poor overall and disease-free survival of 186 patients with CRC. A combination of high CXCL8 and high TOPK expressions had the worst prognosis. We showed that CXCL8 expression was negatively correlated with anoikis in CRC cells. CXCL8 treatment enhanced the resistance of CRC cells to apoptosis, which was accompanied by the increase of TOPK, and the activation of AKT and ERK. Moreover, we demonstrated that the inhibition of either ERK or AKT by specific chemical inhibitors attenuated the CXCL8-mediated resistance to anoikis. Treatment with AKT inhibitor abolished the effects of CXCL8 on TOPK expression, suggesting that TOPK was downstream of AKT in the process of anoikis. Taken together, we demonstrated that CXCL8 is strongly implicated in the resistance of CRC cells to anoikis, and that the AKT, TOPK and ERK pathway may be a potential therapeutic target for CRC.


Assuntos
Anoikis , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Interleucina-8/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Feminino , Imunofluorescência , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Adulto Jovem
18.
J Cancer Res Clin Oncol ; 141(2): 189-201, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24965746

RESUMO

Movement of tumor cells from a primary tumor to a nonadjacent or distant site is a contiguous and complex process. Among the multiple natural cellular programs that promote initiation and progression of tumor metastasis, epithelial-mesenchymal transition (EMT) may play a key role in the ultimate generation of a metastatic foci. Acquisition of the EMT phenotype by tumor cells not only increases their migration and invasion potentials, thereby facilitating their ability to infiltrate blood vessels and to produce circulating tumor cells (CTCs), but also promotes survival of CTCs in the bloodstream and their ability to extravasate out of the circulatory system and invade proximal tissues. In organs distal to the primary tumor, the phenotypic switching mechanism of mesenchymal-epithelial transition (MET) enables CTCs to grow and colonize, enhancing the likelihood of establishing metastasis. In addition, CTCs that have undergone EMT attain increased resistance to chemotherapy and targeted therapy. CTCs with the EMT phenotype have become recognized as an active source of metastases, and targeting EMT/MET processes during the individual steps of tumor metastasis represents a promising new approach for alleviating cancer metastasis and recurrence. In this article, we focus on the biological and clinical importance of EMT and/or MET in CTCs during the individual steps of tumor metastasis, summarizing the recent findings of the regulatory roles played by EMT and/or MET in the generation, survival, and recolonization of CTCs and discussing the EMT-targeting strategies developed for tumor diagnosis as well as their potential for management of metastatic malignant diseases.


Assuntos
Biomarcadores Tumorais/análise , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Animais , Humanos , Metástase Neoplásica , Neoplasias/tratamento farmacológico
19.
In Vitro Cell Dev Biol Anim ; 50(10): 899-908, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25148823

RESUMO

To investigate the effects of icaritin, an active ingredient extracted from Epimedium Sagittatum (Sieb. et Zucc.), on CCl4-induced liver injury and its possible mechanisms. Hepatocytes isolated from Sprague-Dawley male rats were treated with 3 mmol/L CCl4 for 24 h to induce acute liver cell injury, then icaritin (0.1, 1, 10, 100 µmol/L, respectively) was administrated to the cells, and estrogen receptor antagonist ICI182,780 (1 µmol/L) was co-treated with 10 µmol/L icaritin. Biochemical parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), and superoxide dismutase (SOD)) and cell apoptosis were detected to evaluate the injury degree. Protein expressions of Bax, Bcl-2, liver fatty acid-binding protein (L-FABP), and peroxisome proliferator-activated receptor-α (PPAR-α) as well as reactive oxygen species (ROS) generation were determined by western blot. Icaritin alleviated CCl4-induced liver cell injury in a concentration-dependent manner and 10 µmol/L was the optimal concentration. Icaritin (10 µmol/L) significantly reduced activities of ALT, AST in cell culture medium and MDA level of the impaired liver cells, but increased the intercellular SOD activity. The apoptotic rate of the impaired liver cells was also decreased by icaritin (10 µmol/L) treatment. Icaritin might exert antioxidative and anti-apoptotic functions via estrogen-like effect, as the ratio of Bcl-2/Bax was significantly increased, while protein expressions of L-FABP and PPAR-α were markedly increased, and this function was blocked by the estrogen receptor antagonist ICI182,780 efficiently. Icaritin may be a promising drug candidate for acute liver injury benefiting from the antioxidative and anti-apoptotic functions via estrogen-like effect.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Estrogênios , Flavonoides/administração & dosagem , Hepatócitos/efeitos dos fármacos , Alanina Transaminase , Animais , Apoptose/efeitos dos fármacos , Aspartato Aminotransferases/metabolismo , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
20.
Oncotarget ; 5(13): 5029-39, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24970807

RESUMO

The human sulfatase 1 (hSulf-1) gene encodes an endosulfatase that functions to inhibit the heparin-binding growth factor signaling, including the basic fibroblast growth factor (bFGF)-mediated pathway, by desulfating the cell surface heparan sulfate proteoglycans (HSPGs). bFGF could stimulate cell cycle progression and inhibit cell apoptosis, this biological effect can be reversed by hSulf-1. However, molecular mechanisms have not been fully reported. In the current study, by reactivation of hSulf-1 expression and function in the hSulf-1-negative hepatocellular carcinoma (HCC) cell lines and HCC xenograft tumors, we found that hSulf-1 blocked the bFGF effect on the promotion of cell cycle and inhibition of apoptosis. The bFGF-stimulated activation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) pathways was suppressed by hSulf-1, which led to a decreased expression of the target genes Cyclin D1 and Survivin, then finally induced cell cycle arrest and apoptosis in HCC cells. Our data suggested that hSulf-1 may be a suitable target for cancer therapy.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Fator 2 de Crescimento de Fibroblastos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Sulfotransferases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ciclina D1/genética , Ciclina D1/metabolismo , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Transdução de Sinais/genética , Sulfotransferases/genética , Survivina , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA