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1.
World J Surg Oncol ; 19(1): 249, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34419064

RESUMO

OBJECTIVE: To retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM). METHODS: Twenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed. RESULTS: By October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant. CONCLUSIONS: The overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application.


Assuntos
Neoplasias da Mama , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Neoplasias da Mama/terapia , Carcinoma Hepatocelular/terapia , Doxorrubicina/análogos & derivados , Feminino , Gelatina , Humanos , Neoplasias Hepáticas/terapia , Prognóstico , Estudos Retrospectivos
2.
BMC Cancer ; 20(1): 718, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746784

RESUMO

BACKGROUND: To observe the medium- and long-term clinical efficacy and safety of radioactive 125I seed implantation for refractory malignant tumours based on CT-guided 3D template-assisted technique. METHODS: Twenty-five patients with refractory malignant tumours who underwent radioactive 125I seed implantation based on CT-guided 3D template-assisted technique were selected. The post-operative adverse reactions were recorded. The number of puncture needles and particles used in the operation, dosimetric parameters, post-operative physical strength scores, and tumour response were statistically analysed. The overall survival time and survival rate were calculated, and the effect and prognosis were assessed. RESULTS: 125I seed implantation was successful in all patients without serious complications. The average number of implanted puncture needles was 17 (19.12 ± 13.00), and the median number of particles was 52 (55.12 ± 32.97). D90 in the post-operative clinical target volume (CTV) (93.24 ± 15.70 Gy) was slightly lower than that in the pre-operative CTV (93.92 ± 17.60 Gy; P > 0.05). The D90 in the post-operative planning target volume (PTV) (142.16 ± 22.25 Gy) was lower than the pre-operative PTV (145.32 ± 23.48 Gy; P > 0.05). The tumour responses at 6 months post-operatively: complete remission (CR), 20% (5/25); partial remission (PR), 48% (12/25); stable disease (SD), 24% (6/25); progressive disease (PD), 8% (2/25); CR + PR, 68% (17/25); and local control rate, 92% (23/25). The 6-, 12-, and 24-month survival rates were 100, 88, and 52%, respectively. The post-operative physical strength score (Karnofsky performance score, KPS) exhibited a gradual trend towards recovery, which rose to the highest value 12 months after implantation and then decreased slightly, but the average score was still > 90 points. There was one intra-operative pneumothorax, and two patients with superficial malignant tumours developed skin ulcerations. Multivariate analysis of prognosis showed that tumour sites and types were independent risk factors affecting survival. The number of needles and particles and template types were not the factors. CONCLUSIONS: 3D template combined with CT-guided radioactive 125I seed implantation can improve the rational distribution of radiation dose in the tumour target area because accurate radioactive 125I particle implantation was achieved. This technique has fewer complications and can further extend the overall survival and improve the quality of life. TRIAL REGISTRATION: Registration number: ChiCTR2000034566 2020/7/10 0:00:00 Retrospectively registered.


Assuntos
Braquiterapia/métodos , Radioisótopos do Iodo/administração & dosagem , Neoplasias/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Braquiterapia/instrumentação , Progressão da Doença , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Dosagem Radioterapêutica , Indução de Remissão , Taxa de Sobrevida , Resultado do Tratamento
3.
Gene ; 694: 102-110, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30716440

RESUMO

Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) contribute to tumorigenesis, progression and recurrence of various malignancies including Gallbladder carcinoma (GBC). Lnc-DILC is reported to be the tumor suppressor gene to play an important role in liver cancer stem cells (CSCs). However, the role of lnc-DILC in GBC remains to be elucidated. Herein, we show that lnc-DILC is upregulated in gallbladder CSCs and GBC patients' tissues. Knockdown of lnc-DILC attenuates the self-renewal, tumorigenicity, proliferation and metastasis of gallbladder CSCs. Mechanistically, lnc-DILC promotes gallbladder CSCs expansion via Wnt/ß-catenin pathway. Special Wnt/ß-catenin inhibitor FH535 diminishes the discrepancy of self-renewal, growth and metastasis between lnc-DILC interference GBC cells and their control cells. In conclusion, lnc-DILC drives gallbladder CSCs self-renewal, tumorigenicity, proliferation and metastasis by activating Wnt/ß-catenin signaling, and may therefore prove to be a potential therapeutic target for GBC patients.


Assuntos
Neoplasias da Vesícula Biliar/genética , RNA Longo não Codificante/genética , Adulto , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , China , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Camundongos , Camundongos Nus , Recidiva Local de Neoplasia/genética , Células-Tronco Neoplásicas/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais/genética , Via de Sinalização Wnt/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
4.
Cancer Med ; 8(2): 712-728, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30656832

RESUMO

Nasopharyngeal carcinoma (NPC) is a common cancer found in the nasopharynx, which plagues countless NPC patients. MicroRNA-372 (miR-372) has been reported to be involved in various tumors. Here, we explored the important role of miR-372 in radiosensitivity, invasion, and metastasis of NPC. Microarray analysis was conducted to search the NPC-related differentially expressed genes (DEGs) and predict the miRs regulating PBK, which suggested that miR-372 could influence the development of NPC via PBK and the p53 signaling pathway. Importantly, miR-372 was observed to target PBK, thus down-regulating its expression. Then, NPC 5-8F and C666-1 cells were selected, and treated with ionization radiation and alteration of miR-372 and PBK expression to explore the functional role of miR-372 in NPC. The expression of miR-372, PBK, Bcl-2, p53, and Bax as well as the extent of Akt phosphorylation were measured. In addition, cell colony formation, cell cycle, proliferation, apoptosis, migration, and invasion were detected. At last, tumor growth and the effect of miR-372 on radiosensitivity of NPC were evaluated. Besides, over-expressed miR-372 down-regulated Bcl-2 and PBK expression and the extent of Akt phosphorylation while up-regulated the expression of p53 and Bax. Additionally, miR-372 over-expression and radiotherapy inhibited cell clone formation, proliferation, tumor growth, migration, invasion, and cell cycle entry, but promoted cell apoptosis. However, the restoration of PBK in NPC cells expressing miR-372 reversed the anti-tumor effect of miR-372 and activation of the p53 signaling pathway. In conclusion, the study shows that up-regulated miR-372 promotes radiosensitivity by activating the p53 signaling pathway via inhibition of PBK.


Assuntos
MicroRNAs , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Tolerância a Radiação/genética , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/radioterapia , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Raios X
5.
Int J Mol Sci ; 19(12)2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30501023

RESUMO

Bacillus amyloliquefaciens FZB42 is a plant growth-promoting rhizobacteria that stimulates plant growth, and enhances resistance to pathogens and tolerance of salt stress. Instead, the mechanistic basis of drought tolerance in Arabidopsis thaliana induced by FZB42 remains unexplored. Here, we constructed an exopolysaccharide-deficient mutant epsC and determined the role of epsC in FZB42-induced drought tolerance in A. thaliana. Results showed that FZB42 significantly enhanced growth and drought tolerance of Arabidopsis by increasing the survival rate, fresh and dry shoot weights, primary root length, root dry weight, lateral root number, and total lateral root length. Coordinated changes were also observed in cellular defense responses, including elevated concentrations of proline and activities of superoxide dismutase and peroxidase, decreased concentrations of malondialdehyde, and accumulation of hydrogen peroxide in plants treated with FZB42. The relative expression levels of drought defense-related marker genes, such as RD29A, RD17, ERD1, and LEA14, were also increased in the leaves of FZB42-treated plants. In addition, FZB42 induced the drought tolerance in Arabidopsis by the action of both ethylene and jasmonate, but not abscisic acid. However, plants inoculated with mutant strain epsC were less able to resist drought stress with respect to each of these parameters, indicating that epsC are required for the full benefit of FZB42 inoculation to be gained. Moreover, the mutant strain was less capable of supporting the formation of a biofilm and of colonizing the A. thaliana root. Therefore, epsC is an important factor that allows FZB42 to colonize the roots and induce systemic drought tolerance in Arabidopsis.


Assuntos
Arabidopsis/microbiologia , Arabidopsis/fisiologia , Bacillus amyloliquefaciens/fisiologia , Secas , Arabidopsis/metabolismo , Biofilmes/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Malondialdeído/metabolismo , Peroxidase/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Polissacarídeos Bacterianos/metabolismo , Superóxido Dismutase/metabolismo
6.
Can J Gastroenterol Hepatol ; 2018: 3767482, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29808160

RESUMO

The important factors of poor survival of gastric cancer (GC) are relapse and metastasis. For further elucidation of the mechanism, a culture system mimicking the microenvironment of the tumor in humans was needed. We established a model of microencapsulated SGC7901 human GC cells and evaluated the effects of coculturing spheres with tumor-associated macrophages (TAMs). SGC7901 cells were encapsulated in alginate-polylysine-sodium alginate (APA) microcapsules using an electrostatic droplet generator. MTT assays showed that the numbers of microencapsulated cells were the highest after culturing for 14 days. Metabolic curves showed consumption of glucose and production of lactic acid by day 20. Immunocytochemistry confirmed that Proliferating Cell Nuclear Antigen (PCNA) and Vascular Endothelial Growth Factor (VEGF) were expressed in microencapsulated SGC7901 cells on days 7 and 14. The expression of PCNA was observed outside spheroids; however, VEGF was found in the entire spheroids. PCNA and VEGF were increased after being cocultured with TAMs. Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) expressions were detected in the supernatant of microencapsulated cells cocultured with TAMs but not in microencapsulated cells. Our study confirms the successful establishment of the microencapsulated GC cells. TAMs can promote PCNA, VEGF, MMP-2, and MMP-9 expressions of the GC cells.


Assuntos
Carcinoma/patologia , Técnicas de Cocultura , Macrófagos , Neoplasias Gástricas/patologia , Microambiente Tumoral , Carcinoma/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Glucose/metabolismo , Humanos , Ácido Láctico/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Modelos Biológicos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Esferoides Celulares/metabolismo , Neoplasias Gástricas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Gene ; 666: 18-26, 2018 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-29621586

RESUMO

Colorectal cancer (CRC) is one of the most common malignant tumors and one of the leading causes of cancer-related death in both men and women. The prognosis of CRC remains poor due to the advanced stage and cancer metastasis at the time of diagnosis. However, the exact mechanism of tumorigenesis in CRC remains unclear. Long non-coding RNAs (lncRNAs), which refer to transcripts longer than 200 nucleotides that are not translated into protein, are known to play important roles in multiple human cancers. Lnc-DILC is reported to be an important tumor suppressor gene and its inactivation is closely associated with liver cancer stem cells. However, the role of lnc-DILC in CRC remains to be elucidated. In the present study, we observed that lnc-DILC overexpression inhibited the growth and metastasis of CRC cells. Consistently, lnc-DILC knockdown facilitated the proliferation and metastasis of CRC cells. Mechanically, lnc-DILC suppressed CRC cell progression via IL-6/STAT3 signaling inactivation. More importantly, the specific STAT3 inhibitor S3I-201 and IL-6R inhibitor tocilizumab abolished the discrepancy of growth and metastasis capacity between lnc-DILC-interference CRC cells and control cells, which further confirmed that IL-6/STAT3 signaling was required in lnc-DILC-disrupted CRC cell growth and metastasis. Taken together, our results suggest that lnc-DILC is a novel CRC suppressor and may prove to be an inhibitor of CRC progression by inactivating IL-6/STAT3 signaling.


Assuntos
Neoplasias Colorretais/genética , RNA Longo não Codificante/fisiologia , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Genes Supressores de Tumor , Células HCT116 , Humanos , Interleucina-6/fisiologia , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
8.
J Gastrointest Surg ; 22(5): 872-883, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29313290

RESUMO

BACKGROUND: Chronic HBV plays an important role in hepatocellular carcinoma pathogenesis. Previously, most studies have been focusing on HBV DNA levels before the primary curative hepatectomy. However, the association of virus level before repeat hepatectomy with the degrees of inflammation and fibrosis on histopathology and prognosis has not been surveyed. METHODS: From January 2002 to December 2009, all patients who were seropositive for hepatitis B surface antigen (HBsAg) were enrolled and assigned into four groups based on their HBV DNA levels before the primary and repeat hepatectomies. The cancer prognoses of these four groups of patients after the first and second operations were assessed and compared. The disease-free survival and overall survival were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify risk factors for the primary and repeat hepatectomies. RESULTS: For the 385 patients in this study, a low level of serum HBV DNA before repeat hepatectomy, but not primary hepatectomy, was significantly associated with improvement in prognosis, in terms of tumor recurrence, liver fibrosis, and liver-related mortality. CONCLUSION: The levels of HBV DNA before hepatectomies were crucial prognostic risk factors of HBV-related hepatocellular carcinoma patients. Surveillance of serum HBV DNA levels at multiple time points, rather than at a single time point, and antiviral therapy to suppress the virus to a low level had beneficial effects for these patients.


Assuntos
Carcinoma Hepatocelular/cirurgia , DNA Viral/sangue , Vírus da Hepatite B , Hepatite B Crônica/sangue , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/sangue , Carga Viral , Carcinoma Hepatocelular/virologia , Intervalo Livre de Doença , Hepatectomia , Hepatite B Crônica/complicações , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Recidiva Local de Neoplasia/virologia , Período Pré-Operatório , Prognóstico , Reoperação , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
9.
Arch Virol ; 163(3): 781-785, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29181623

RESUMO

Infection with shrimp hemocyte iridescent virus (SHIV), a new virus of the family Iridoviridae isolated in China, results in a high mortality rate in white leg shrimp (Litopenaeus vannamei). The complete genome sequence of SHIV was determined and analyzed in this study. The genomic DNA was 165,809 bp long with 34.6% G+C content and 170 open reading frames (ORFs). Dotplot analysis showed that the longest repetitive region was 320 bp in length, including 11 repetitions of an 18-bp sequence and 3.1 repetitions of a 39-bp sequence. Two phylogenetic trees were constructed based on 27 or 16 concatenated sequences of proteins encoded by genes that are conserved between SHIV homologous and other iridescent viruses. The results of this study, suggest that SHIV should be considered a member of the proposed new genus "Xiairidovirus".


Assuntos
DNA Viral/genética , Genoma Viral , Iridovirus/genética , Penaeidae/virologia , Filogenia , Animais , Composição de Bases , Sequência de Bases , Hemócitos/virologia , Iridovirus/classificação , Iridovirus/isolamento & purificação , Fases de Leitura Aberta , Análise de Sequência de DNA
10.
Sci Rep ; 7(1): 11834, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28928367

RESUMO

A newly discovered iridescent virus that causes severe disease and high mortality in farmed Litopenaeus vannamei in Zhejiang, China, has been verified and temporarily specified as shrimp hemocyte iridescent virus (SHIV). Histopathological examination revealed basophilic inclusions and pyknosis in hematopoietic tissue and hemocytes in gills, hepatopancreas, periopods and muscle. Using viral metagenomics sequencing, we obtained partial sequences annotated as potential iridoviridae. Phylogenetic analyses using amino acid sequences of major capsid protein (MCP) and ATPase revealed that it is a new iridescent virus but does not belong to the five known genera of Iridoviridae. Transmission electron microscopy showed that the virus exhibited a typical icosahedral structure with a mean diameter of 158.6 ± 12.5 nm (n = 30)(v-v) and 143.6 ± 10.8 nm (n = 30)(f-f), and an 85.8 ± 6.0 nm (n = 30) nucleoid. Challenge tests of L. vannamei via intermuscular injection, per os and reverse gavage all exhibited 100% cumulative mortality rates. The in situ hybridization showed that hemopoietic tissue, gills, and hepatopancreatic sinus were the positively reacting tissues. Additionally, a specific nested PCR assay was developed. PCR results revealed that L. vannamei, Fenneropenaeus chinensis, and Macrobrachium rosenbergii were SHIV-positive, indicating a new threat existing in the shrimp farming industry in China.


Assuntos
Aquicultura , Iridoviridae , Penaeidae/virologia , Filogenia , Animais , Iridoviridae/classificação , Iridoviridae/genética , Iridoviridae/isolamento & purificação , Iridoviridae/metabolismo
11.
Gastroenterology ; 152(5): 1187-1202, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28065789

RESUMO

BACKGROUND & AIMS: Choline kinase α (CHKA) catalyzes conversion of choline to phosphocholine and can contribute to carcinogenesis. Little is known about the role of CHKA in the pathogenesis of hepatocellular carcinoma (HCC). METHODS: We performed whole-exome and transcriptome sequence analyses of 9 paired HCC and non-tumor-adjacent tissues. We performed tissue chip analyses of 120 primary HCC and non-tumor-adjacent tissues from patients who received surgery in Shanghai, China from January 2006 through December 2009; 48 sets of specimens (HCC and non-tumor-adjacent tissues) were also analyzed. CHKA gene copy number was quantified and findings were validated by quantitative reverse transcription polymerase chain reaction analysis. CHKA messenger RNA and protein levels were determined by polymerase chain reaction, immunohistochemical, and immunoblot analyses. CHKA was examined in 2 hepatocyte cell lines and 7 HCC-derived cell lines, and knocked down with small interfering RNAs in 3 HCC cell lines. Cells were analyzed in proliferation, wound healing, migration, and invasion assays. Cells were injected into tail veins of mice and tumor growth and metastasis were quantified. Immunoprecipitation and immunofluorescence assays were conducted to determine interactions between CHKA and the epidermal growth factor receptor (EGFR) and the mechanistic target of rapamycin complex 2. RESULTS: Levels of CHKA messenger RNA were frequently increased in HCC tissues compared with nontumor tissues; increased expression was associated with amplification at the CHKA loci. Tumors that expressed high levels of CHKA had more aggressive phenotypes, and patients with these tumors had shorter survival times after surgery compared to patients whose tumors expressed low levels of CHKA. HCC cell lines that stably overexpressed CHKA had higher levels of migration and invasion than control HCC cells, and formed larger xenograft tumors with more metastases in mice compared to HCC cells that did not overexpress CHKA. CHKA was required for physical interaction between EGFR and mechanistic target of rapamycin complex 2. This complex was required for HCC cells to form metastatic xenograft tumors in mice and to become resistant to EGFR inhibitors. CONCLUSIONS: We found levels of CHKA to be increased in human HCCs compared to nontumor tissues, and increased expression to be associated with tumor aggressiveness and reduced survival times of patients. Overexpression of CHKA in HCC cell lines increased their invasiveness, resistance to EGFR inhibitors, and ability to form metastatic tumors in mice by promoting interaction of EGFR with mechanistic target of rapamycin complex 2.


Assuntos
Carcinoma Hepatocelular/metabolismo , Colina Quinase/genética , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/metabolismo , Neoplasias Hepáticas/metabolismo , Complexos Multiproteicos/metabolismo , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/genética , Colina Quinase/metabolismo , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/farmacologia , Gefitinibe , Células Hep G2 , Humanos , Immunoblotting , Imuno-Histoquímica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Alvo Mecanístico do Complexo 2 de Rapamicina , Camundongos , Invasividade Neoplásica/genética , Transplante de Neoplasias , Quinazolinas/farmacologia , Cicatrização/genética , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Nat Commun ; 7: 12992, 2016 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-27703150

RESUMO

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Vírus da Hepatite B/fisiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Transformação Celular Neoplásica , Ilhas de CpG , DNA Viral/genética , Feminino , Genoma Humano , Genoma Viral , Hepatite B Crônica/genética , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/genética , Cirrose Hepática/virologia , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Análise de Sequência de RNA , Integração Viral
14.
PLoS One ; 11(8): e0158621, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27513952

RESUMO

Some plant growth-promoting rhizobacteria (PGPR) regulated plant growth and elicited plant basal immunity by volatiles. The response mechanism to the Bacillus amyloliquefaciens volatiles in plant has not been well studied. We conducted global gene expression profiling in Arabidopsis after treatment with Bacillus amyloliquefaciens FZB42 volatiles by Illumina Digital Gene Expression (DGE) profiling of different growth stages (seedling and mature) and tissues (leaves and roots). Compared with the control, 1,507 and 820 differentially expressed genes (DEGs) were identified in leaves and roots at the seedling stage, respectively, while 1,512 and 367 DEGs were identified in leaves and roots at the mature stage. Seventeen genes with different regulatory patterns were validated using quantitative RT-PCR. Numerous DEGs were enriched for plant hormones, cell wall modifications, and protection against stress situations, which suggests that volatiles have effects on plant growth and immunity. Moreover, analyzes of transcriptome difference in tissues and growth stage using DGE profiling showed that the plant response might be tissue-specific and/or growth stage-specific. Thus, genes encoding flavonoid biosynthesis were downregulated in leaves and upregulated in roots, thereby indicating tissue-specific responses to volatiles. Genes related to photosynthesis were downregulated at the seedling stage and upregulated at the mature stage, respectively, thereby suggesting growth period-specific responses. In addition, the emission of bacterial volatiles significantly induced killing of cells of other organism pathway with up-regulated genes in leaves and the other three pathways (defense response to nematode, cell morphogenesis involved in differentiation and trichoblast differentiation) with up-regulated genes were significantly enriched in roots. Interestingly, some important alterations in the expression of growth-related genes, metabolic pathways, defense response to biotic stress and hormone-related genes were firstly founded response to FZB42 volatiles.


Assuntos
Arabidopsis/genética , Bacillus amyloliquefaciens/fisiologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/genética , Plântula/genética , Transcriptoma , Compostos Orgânicos Voláteis/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA de Plantas/genética , Plântula/efeitos dos fármacos , Plântula/metabolismo
15.
Oncotarget ; 7(41): 66660-66678, 2016 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-27556502

RESUMO

Aberrant expression of choline kinase alpha (CHKA) has been reported in a variety of human malignancies including colorectal carcinoma (CRC). However, the role of CHKA in the progression and prognosis of CRC remains unknown. In this study, we found that CHKA was frequently upregulated in CRC clinical samples and CRC-derived cell lines and was significantly correlated with lymph node metastasis (p = 0.028), TNM stage (p = 0.009), disease recurrence (p = 0.004) and death (p < 0.001). Survival analyses indicated that patients with higher CHKA expression had a significantly shorter disease-free survival (DFS) and disease-specific survival (DSS) than those with lower CHKA expression. Multivariate analyses confirmed that increased CHKA expression was an independent unfavorable prognostic factor for CRC patients. In addition, combination of CHKA with TNM stage was a more powerful predictor of poor prognosis than either parameter alone. Functional study demonstrated that knockdown of CHKA expression profoundly suppressed the growth and metastasis of CRC cells both in vitro and in vivo. Mechanistic investigation revealed that EGFR/PI3K/AKT pathway was essential for mediating CHKA function. In conclusion, our results provide the first evidence that CHKA contributes to tumor progression and metastasis and may serve as a novel prognostic biomarker and potential therapeutic target in CRC.


Assuntos
Colina Quinase/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Proliferação de Células/genética , Colina Quinase/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Células HCT116 , Células HT29 , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Interferência de RNA , Adulto Jovem
16.
Oncotarget ; 7(24): 37238-37249, 2016 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-27191988

RESUMO

Zinc finger CCCH-type containing 15 (ZC3H15), also known as DRG family regulatory protein 1 (DFRP1), is a highly conserved eukaryotic protein that associates with active translation machinery. The aim of our study was to explore the clinical relevance and intrinsic functions of ZC3H15 in hepatocellular carcinoma (HCC). We constructed a cohort with 261 tumor and matched normal tissues from HCC patients. ZC3H15 protein and mRNA levels were determined using immunohistochemistry, western blot analysis, and quantitative polymerase chain reaction. ZC3H15 was highly expressed in the majority of HCC cases, and high ZC3H15 levels were significantly associated with high serum a-fetoprotein (AFP) levels (>20 ng/mL) and vascular invasion. Kaplan-Meier and Cox regression data indicated that elevated ZC3H15 was an independent predictor for HCC-specific disease-free survival (hazards ratio [HR], 1.789; 95% confidence interval [95% CI], 1.298-2.466 [P=0.0004]) and overall survival (HR, 1.613; 95% CI, 1.120-2.322 [P=0.0101]). Interaction of ZC3H15 with TRAF2 increased activation of NFκB signaling. These results suggest ZC3H15 is an independent prognostic marker in HCC patients that is clinicopathologically associated with tumor invasion and serum AFP levels.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Adulto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Western Blotting , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Proteínas de Transporte/genética , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Invasividade Neoplásica , Prognóstico , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Transdução de Sinais , Fator 2 Associado a Receptor de TNF/metabolismo , Análise Serial de Tecidos , alfa-Fetoproteínas/análise
17.
Chin Med J (Engl) ; 129(5): 594-600, 2016 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-26904995

RESUMO

OBJECTIVE: To review the recent developments in the mechanisms of epithelium sodium channels (ENaCs) induced bone formation and regulation. DATA SOURCES: Studies written in English or Chinese were searched using Medline, PubMed and the index of Chinese-language literature with time restriction from 2005 to 2014. Keywords included ENaC, bone, bone formation, osteonecrosis, estrogen, and osteoporosis. Data from published articles about the structure of ENaC, mechanism of ENaC in bone formation in recent domestic and foreign literature were selected. STUDY SELECTION: Abstract and full text of all studies were required to obtain. Studies those were not accessible and those did not focus on the keywords were excluded. RESULTS: ENaCs are tripolymer ion channels which are assembled from homologous α, ß, and γ subunits. Crystal structure of ENaCs suggests that ENaC has a central ion-channel located in the central symmetry axis of the three subunits. ENaCs are protease sensitive channels whose iron-channel activity is regulated by the proteolytic reaction. Channel opening probability of ENaCs is regulated by proteinases, mechanical force, and shear stress. Several molecules are involved in regulation of ENaCs in bone formation, including nitride oxide synthases, voltage-sensitive calcium channels, and cyclooxygenase-2. CONCLUSION: The pathway of ENaC involved in shear stress has an effect on stimulating osteoblasts even bone formation by estrogen interference.


Assuntos
Canais Epiteliais de Sódio/fisiologia , Osteogênese/fisiologia , Canais de Cálcio/fisiologia , Canais Epiteliais de Sódio/química , Estrogênios/farmacologia , Humanos
18.
World J Surg Oncol ; 14(1): 10, 2016 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-26762567

RESUMO

BACKGROUND: The invasion of colon cancer is associated with the tumor angiogenesis. Endostatin is an important anti-angiogenic agent, and the additive effect of endostatin with a chemotherapeutic agent, cyclophosphamide, on micrangium has not been established. METHODS: Male BALB/c strain nude mice were injected with human colorectal carcinoma cells (HCT-116). The mice were divided into four groups (n=15, each group) and were treated with different concentrations of endostatin (15, 10, and 5 mg/kg/day), cyclophosphamide (20, 10, and 5 mg/kg/day), and combination of endostatin/cyclophosphamide (15+20, 15+10, and 15+5 mg/kg/day). The tumor inhibition rate was evaluated, followed by the quantification of messenger ribonucleic acid (mRNA) and protein expression of notch signaling components NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, DLL-4, Hes-1, and Hey-1 using quantitative polymerase chain reaction (qPCR). The protein expression of NOTCH-3, JAG-1, and DLL-4 was confirmed using western blotting. Microvessel density (MVD) was evaluated to detect micrangium following the treatment. RESULTS: The endostatin/cyclophosphamide-treated samples exhibited an additive effect on the tumor inhibition rate and the microvessel count. NOTCH-1, NOTCH-3, NOTCH-4, JAG-1, Hes-1, and Hey-1 expression levels were highly correlated and downregulated in the treated samples, whereas DLL-4 expression was upregulated that accounted for its anti-angiogenic property. CONCLUSIONS: The combination treatment of colon cancer with endostatin and a chemotherapeutic agent, cyclophosphamide proves to be an efficient therapeutic strategy to inhibit the rapid vasculature formation confirmed by the differential expression of notch signaling components.


Assuntos
Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias do Colo/tratamento farmacológico , Ciclofosfamida/farmacologia , Endostatinas/farmacologia , Microvasos/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Western Blotting , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Endostatinas/uso terapêutico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Reação em Cadeia da Polimerase , Distribuição Aleatória , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Medicine (Baltimore) ; 94(40): e1344, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26447993

RESUMO

Previous studies showed that suppressor of cytokine signaling 3 (SOCS3) protein is associated with incidence and progression of hepatocellular carcinoma (HCC); however, the association between the genetic polymorphism of SOCS3 gene and HCC remains unknown. A total of 254 HCC patients and 354 healthy controls were enrolled. All HCC patients underwent partial hepatectomy as initial treatment and were followed. Three SOCS3 gene polymorphisms, namely, rs4969170 A>G, rs8064821 C>T, and rs12953258 C>A were determined. Our data show that the rs4969170 A>G polymorphism dramatically affects the susceptibility to HCC in our cohorts. Logistic regression analyses revealed that the rs4969170 GG is a risk factor for HCC after the adjustment with confounding factors. The rs4969170A>G polymorphism is also associated with the clinical features of HCC patients and predicts the postoperative relapse-free survival and overall survival. The rs4969170GG genotype carrier had a worse prognosis than the rs4969170AG and rs4969170AA carrier. Our findings suggest that the rs4969170A>G polymorphism of SOCS3 gene may be used as a prognostic predictor for HCC patients who underwent surgical treatment.


Assuntos
Carcinoma Hepatocelular/genética , Hepatectomia , Neoplasias Hepáticas/genética , Polimorfismo Genético , Proteínas Supressoras da Sinalização de Citocina/genética , Western Blotting , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/terapia , Feminino , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteína 3 Supressora da Sinalização de Citocinas
20.
J Hepatol ; 63(3): 651-60, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25865556

RESUMO

BACKGROUND & AIMS: We have previously reported that Shp2, a tyrosine phosphatase previously known as a pro-leukemogenic molecule, suppresses the initiation of hepatocellular carcinoma (HCC). However, the role of Shp2 in HCC progression remains obscure. METHODS: Shp2 expression was determined in human HCC using real-time PCR, immunoblotting and immunohistochemistry. Clinical significance of Shp2 expression was analyzed in 301 HCC tissues with clinico-pathological characteristics and follow-up information. Short hairpin RNA was utilized to investigate the function of Shp2 in hepatoma cell behavior. Role of Shp2 in HCC progression was monitored through nude mice xenograft assay. Kinase activity assay and co-immunoprecipitation were used for mechanism analysis. RESULTS: Elevated expression of Shp2 was detected in 65.9% (394/598) of human HCCs, and its levels were even higher in metastasized foci. Overexpression of Shp2 correlated well with the malignant clinico-pathological characteristics of HCC and predicted the poor prognosis of patients. Interference of Shp2 expression suppressed the proliferation of hepatoma cells in vitro and inhibited the growth of HCC xenografts in vivo. Down-regulation of Shp2 attenuated the adhesion and migration of hepatoma cells and diminished metastasized HCC formation in mice. Our data demonstrated that Shp2 promotes HCC growth and metastasis by coordinately activating Ras/Raf/Erk pathway and PI3-K/Akt/mTOR cascade. Moreover, down-regulation of Shp2 enhanced the sensitivity of hepatoma cells upon sorafenib treatment, and patients with low Shp2 expression exhibited superior prognosis to sorafenib. CONCLUSIONS: Shp2 promotes the progression of HCC and may serve as a prognostic biomarker for patients.


Assuntos
Carcinoma Hepatocelular/etiologia , Neoplasias Hepáticas/etiologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/fisiologia , Animais , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Humanos , Neoplasias Hepáticas/mortalidade , Sistema de Sinalização das MAP Quinases , Camundongos , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Compostos de Fenilureia/farmacologia , Fosfatidilinositol 3-Quinases/fisiologia , Prognóstico , Sorafenibe , Quinases raf/fisiologia
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