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1.
Oncotarget ; 8(34): 57337-57344, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28915674

RESUMO

Bevacizumab, as antibodies, were applied to inhibit tumor angiogenesis by preventing activation of vascular endothelial growth factor receptor. We analyzed four clinical trials, including 607 patients, to investigate the efficacy and safety of bevacizumab when combined with chemotherapy for the treatment of glioblastomas. Results demonstrated that bevacizumab when combined with chemotherapy improved progression-free survival (HR = 0.66; 95% CI 0.56-0.78; p < 0.00001) compared with bevacizumab or chemotherapy alone. Furthermore, overall survival showed insignificant difference between two arms (HR 0.99; 95% CI 0.8-1.21; p = 0.92). However, we found that patients treated with bevacizumab-containing therapy reported increased objective response rate (OR 1.85, 95% CI 1.17-2.93; p = 0.009), but more treatment-related adverse events (OR 1.75; 95% CI 1.09-2.83; p = 0.02).

2.
Oncotarget ; 6(29): 26971-81, 2015 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-26284486

RESUMO

Glioma is a most common type of primary brain tumors. Extracellular vesicles, in the form of exosomes, are known to mediate cell-cell communication by transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we examined the cerebrospinal fluid (CSF) from patients with recurrent glioma for the levels of cancer-related miRNAs, and evaluated the values for prognosis by comparing the measures of CSF-, serum-, and exosome-contained miR-21 levels. Samples from seventy glioma patients following surgery were compared with those from brain trauma patients as a non-tumor control group. Exosomal miR-21 levels in the CSF of glioma patients were found significantly higher than in the controls; whereas no difference was detected in serum-derived exosomal miR-21 expression. The CSF-derived exosomal miR-21 levels correlated with tumor spinal/ventricle metastasis and the recurrence with anatomical site preference. From additional 198 glioma tissue samples, we verified that miR-21 levels associated with tumor grade of diagnosis and negatively correlated with the median values of patient overall survival time. We further used a lentiviral inhibitor to suppress miR-21 expression in U251 cells. The results showed that the levels of miR-21 target genes of PTEN, RECK and PDCD4 were up-regulated at protein levels. Therefore, we concluded that the exosomal miR-21 levels could be demonstrated as a promising indicator for glioma diagnosis and prognosis, particularly with values to predict tumor recurrence or metastasis.


Assuntos
Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/líquido cefalorraquidiano , Exossomos/metabolismo , Glioma/sangue , Glioma/líquido cefalorraquidiano , MicroRNAs/metabolismo , Adulto , Idoso , Proteínas Reguladoras de Apoptose/metabolismo , Astrocitoma/sangue , Astrocitoma/líquido cefalorraquidiano , Astrocitoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico , Linhagem Celular Tumoral , Progressão da Doença , Ependimoma/sangue , Ependimoma/líquido cefalorraquidiano , Ependimoma/diagnóstico , Feminino , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/sangue , Glioblastoma/líquido cefalorraquidiano , Glioblastoma/diagnóstico , Glioma/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Lentivirus/genética , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , PTEN Fosfo-Hidrolase/metabolismo , Prognóstico , Proteínas de Ligação a RNA/metabolismo , Curva ROC , Recidiva , Fatores de Tempo
3.
Int J Clin Exp Med ; 8(4): 4883-98, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26131062

RESUMO

BACKGROUND: There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. METHODS: All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. RESULTS: The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. CONCLUSION: The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 37(1): 23-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25676266

RESUMO

OBJECTIVE: To investigate the whole genome expression profiles between gastric high-grade intraepithelial neoplasia (HGIN) tissues with cancer and HGIN tissues without cancer. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected at Peking Union Medical College Hospital from March 2010 to May 2013. Each of the forceps biopsies from the 21 patients was HGIN,but there were 10 HGIN and 11 HGIN with cancer after the endoscopic submucosal dissection. The whole genome expression profiling was performed on 10 HGIN samples and 11 HGIN with cancer samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology(GO)enrichment analysis was performed using the GeneSpring software GX 12.6. RESULTS: The gene expression patterns were different between HGIN tissues with cancer and HGIN tissues without cancer. There were 470 significantly differentially expressed transcripts between them (P<0.05,Fold Change>2), with 180 up-regulated genes and 290 down-regulated genes in HGIN tissues with cancer. A GO enrichment analysis demonstrated that the most striking over-expressed transcripts in HGIN with cancer were in the category of triglyceride biosynthetic process,acylglycerol biosynthetic process,neutral lipid biosynthetic process,glycerol ether metabolic process,organic ether metabolic process,and glycerolipid metabolic process. CONCLUSION: The change of lipid metabolism may contribute to the pathogenesis of gastric cancer at an early stage.


Assuntos
Regulação Neoplásica da Expressão Gênica , Genoma Humano , Gastropatias , Neoplasias Gástricas , Algoritmos , Regulação para Baixo , Humanos , Metabolismo dos Lipídeos , Software , Regulação para Cima
5.
World J Gastroenterol ; 20(47): 17883-93, 2014 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-25548486

RESUMO

AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013. Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia (LGIN), 20 high-grade intraepithelial neoplasia (HGIN), 19 early-stage adenocarcinoma (EGC), and 19 chronic gastritis tissue samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology (GO) enrichment analysis was performed using the GeneSpring software GX 12.6. The differentially expressed gene was verified using a real-time TaqMan® PCR assay with independent tissue samples, including 26 LGIN, 15 HGIN, 14 EGC, and 20 chronic gastritis. The expression of G0S2 were further validated by immunohistochemical staining (IHC) in 24 LGIN, 40 HGIN, 30 EGC and 61 chronic gastritis specimens. RESULTS: The gene expression patterns of LGIN and HGIN tissues were distinct. There were 2521 significantly differentially expressed transcripts in HGIN, with 951 upregulated and 1570 downregulated. A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism, defense response, and nuclear factor κB (NF-κB) cascade. While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues, only 38 transcripts were upregulated in EGC. A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC. It is worth noting that, compared with LGIN, 289 transcripts were expressed at higher levels both in HGIN and EGC. A characteristic gene, G0/G1 switch 2 (G0S2) was one of the 289 transcripts and related to metabolism, the immune response, and the NF-κB cascade, and its expression was validated in independent samples through real-time TaqMan® PCR and immunohistochemical staining. In real-time PCR analysis, the expression of G0S2 was elevated both in HGIN and EGC compared with that in LGIN (P < 0.01 and P < 0.001, respectively). In IHC analysis, G0S2 immunoreactivity was detected in the cytoplasmic of neoplastic cells, but was undetectable in chronic gastritis cells. The G0S2 expression in HGIN was higher than that of LGIN (P = 0.012, χ (2) = 6.28) and EGC (P = 0.008, χ (2) = 6.94). CONCLUSION: A clear biological distinction between gastric high- and low-grade intraepithelial neoplasia was identified, and provides molecular evidence for clinical application.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Carcinoma in Situ/genética , Perfilação da Expressão Gênica , Neoplasias Gástricas/genética , Adenocarcinoma/química , Adenocarcinoma/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Biópsia , Carcinoma in Situ/química , Carcinoma in Situ/patologia , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/genética , Biologia Computacional , Bases de Dados Genéticas , Diagnóstico Diferencial , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/química , Neoplasias Gástricas/patologia , Transcrição Genética
6.
Fam Cancer ; 13(3): 361-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24664542

RESUMO

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease caused by a mutation in the adenomatous polyposis coli (APC) gene. Some studies have attempted to correlate mutations at codon 1309 with classic FAP (≥100 colorectal polyps). We report two Chinese FAP pedigrees with new frameshift mutations at codon 1309, in which affected individuals manifest phenotypic variations. Comprehensive physical examinations were performed for all living individuals and the medical data of deceased patients were collected. Screening of the APC and human mutY homolog (MUTYH) genes for germline mutations was conducted by direct polymerase chain reaction (PCR) sequencing. In two pedigrees, a heterozygous deletion in exon 16 of the APC gene was present in all FAP patients but absent in the unaffected individuals. There were no changes to the MUTYH gene. The first pedigree, with a new frameshift mutation at c.3926_3930 del AAAAG (p. Glu1309Aspfs X4), exhibited obvious differences in the polyp number such that the proband manifested only three colorectal polyps, whereas another patients showed the symptoms of classic FAP. The second pedigree, also traced a new mutation at c.3922_3925 del AAAG (p. Glu1309Argfs X11). Although all of the patients presented with classic polyposis, one of them exhibited a delayed onset of colorectal cancer in his 50s. Two novel mutations at codon 1309 in two Chinese families suffering from FAP could enrich the germline mutation spectrum of the APC gene. Families of individuals might manifest different phenotypes, even with an identical codon 1309 mutation, unlike in previous studies.


Assuntos
Polipose Adenomatosa do Colo/genética , Genes APC , Predisposição Genética para Doença/genética , Mutação , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Sequência de Bases , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Fenótipo , Reação em Cadeia da Polimerase
7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 47(8): 752-6, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-24246084

RESUMO

OBJECTIVE: To analysis the molecular interaction network of 14-3-3 sigma in non small cell lung cancer (NSCLC) cells. METHODS: Established stable over-expressed 14-3-3 sigma protein PG cells, MTT assay was used to assess the growth rate of PG cells. Though stable isotope labeling by amino acids in cell culture (SILAC) and Mass spectrometry (MS) technology, to identify difference expressed proteins caused by over expressed 14-3-3 sigma. The protein expressed >2 or <0.5 times was termed as the differential protein. By searching Human protein reference database (HPRD) and Kyoto encyclopedia of genes and genomes (KEGG), established the molecular interaction network of tumor suppressor gene 14-3-3 sigma. RESULTS: The growth rate of over-expressed 14-3-3 sigma PG cell was obviously slower down compared to vector PG cells. A database including 147 differential protein was established. And a molecular interaction network of 14-3-3 sigma containing 26 protein was constructed.In this network, the expression of CSNK2A1 (casein kinase II subunit alpha), involved in numerous cellular processes, such as cell cycle progression, apoptosis and transcription, was the most significantly increased. A DNA repair protein, MEN1 (Menin) which functions as a transcriptional regulator was the most significantly decreased. CONCLUSION: After stable transfected with 14-3-3 sigma gene, growth rate of PG cells was inhibited, the proteins associated with cell cycle, DNA damage repair mechanisms were significantly changed, and constructed the molecular interaction network.


Assuntos
Proteínas 14-3-3/genética , Biomarcadores Tumorais/genética , Exorribonucleases/genética , Neoplasias Pulmonares/genética , Aminoácidos , Carcinoma Pulmonar de Células não Pequenas/genética , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Marcação por Isótopo/métodos , Espectrometria de Massas , Transfecção
8.
Med Oncol ; 28(1): 336-41, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20237870

RESUMO

This study was designed to evaluate the expression of C-erbB-2 and p16 in lung cancers using tissue microarray technology and to determine their clinical and pathological significance. Immunohistochemical C-erbB-2 and p16 expressions and their associations with clinical and pathological features were analyzed in two tissue microarrays. The membranous and cytoplasmic expression rates of C-erbB-2 were 40.5 and 66.5% in non-small cell lung cancers (NSCLCs), and 0 and 9.5% in small cell lung cancers (SCLCs), respectively. The nuclear and cytoplasmic expression rates of p16 were 11.5 and 32.2% in NSCLs, and 45 and 80% in SCLCs, respectively. The cytoplasmic expression of both C-erbB-2 and p16 was more frequent than the membranous expression of C-erbB-2 and the nuclear expression of p16. The rates of overexpression of C-erbB-2 and loss of p16 expression were significantly higher in NSCLCs than in SCLCs (P < 0.05). Neither C-erbB-2 nor p16 expression was significantly associated with age, tumor grade or stage, presence of lymph node metastasis or survival duration. The abnormal expressions of p16 and C-erbB-2 may play a role in the progression of lung cancers. The variations in the expression patterns of C-erbB-2 and p16 between NSCLCs and SCLCs may aid the molecular classification of lung cancer. The abnormal expression of p16 may be involved in the development of NSCLCs, and the overexpression of C-erbB-2 in NSCLCs indicates that it can be a candidate target for gene therapy.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Neoplasias Pulmonares/metabolismo , Receptor ErbB-2/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Adenocarcinoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Pulmonares/diagnóstico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Patologia Molecular , Prognóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico
10.
Oncol Rep ; 17(5): 1083-8, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17390048

RESUMO

Aurora-A/BTAK/STK15 gene which encodes a centrosome-associated kinase is located on chromosome 20q13.2, a highly amplified region in various human tumors. Recent studies have demonstrated the overexpression and amplification of Aurora-A in many malignant human cancers. The purpose of this study was to investigate the amplification and expression of Aurora-A in esophageal squamous cell carcinoma. Amplification of Aurora-A was determined by fluorescence in situ hybridization in 7 esophageal cancer cell lines and real-time PCR in 29 esophageal cancer samples. We detected Aurora-A expression in 7 esophageal cancer cell lines and 38 esophageal cancers samples by semi-quantitative reverse transcription-PCR and Western blot hybridization. The amplification of Aurora-A was detected in 27 of 29 (93.1%) esophageal cancer samples and 6 of 7 (85.7%) cancer cell lines. Aurora-A was overexpressed in 27 of 38 (71.1%) esophageal cancer samples and all 7 esophageal cancer cell lines. We conclude that Aurora-A is amplified and overexpressed in esophageal squamous cancer.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteínas Serina-Treonina Quinases/genética , Aurora Quinase A , Aurora Quinases , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Sondas de DNA , Neoplasias Esofágicas/metabolismo , Amplificação de Genes , Dosagem de Genes , Humanos , Hibridização in Situ Fluorescente , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Zhonghua Zhong Liu Za Zhi ; 29(8): 591-5, 2007 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-18210878

RESUMO

OBJECTIVE: Data obtained from a differentially expressed cDNA library constructed previously in this laboratory demonstrated that the extracellular matrix molecule osteopontin (OPN) is one of most considerably over-expressed genes in non-small cell lung cancers (NSCLCs). The purpose of the present study was to explore the expression status of OPN in a large scale NSCLC tissue samples, and estimate its significance in progression of the malignant disease. METHODS: RT-PCR was performed with the tumor and adjacent normal tissues from 35 patients with NSCLC, at transcriptional levels of OPN. To determine the expression of OPN protein in the tumor tissues, immunohistochemical (IHC) staining was subsequently carried out on paraffin-embedded sections in tissue microarrays containing 662 samples derived from NSCLC cases. The correlation between the expression level of OPN and clinical characteristics was analyzed statistically. RESULTS: Comparing with the paired normal lung tissue, high level RNA of OPN was detected in 80.0% (28/35) of the NSCLC tumor tissues by RT-PCR, which confirmed the information obtained previously by our differentially expressed cDNA library. The results of IHC analysis showed that positively stained OPN protein was observed in 59.6% (331/555) of the tumor tissues, which was remarkably higher than that (25.2%, 27/107) detected in the normal control tissues (P < 0.001). Among the NSCLCs investigated, over-expressed OPN was more frequently found in squamous cell carcinomas (SCCs) than in adenocarcinomas. A further analysis on SCCs demonstrated that the rate of over-expressed OPN was significantly different between the primary tumors with and without lymphatic metastases (68.6% vs. 49.7%, P = 0.001), but similar in the primary tumors and their corresponding metastases in lymph nodes (68.6% vs. 75.5%, P = 0.171). CONCLUSION: Expression of OPN protein is distinctly increased in NSCLCs, particularly in SCCs. OPN over-expression is considerably correlated with lymph node metastasis, increasing the risk of tumor metastasis (OR = 2.212). The resulting data suggest that OPN facilitates the progression of NSCLCs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Osteopontina/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Osteopontina/genética , Regulação para Cima
12.
Zhonghua Bing Li Xue Za Zhi ; 35(9): 540-4, 2006 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-17134548

RESUMO

OBJECTIVE: To study the expression of targeting protein for Xklp2 (TPX2) and its significance in squamous cell carcinoma (SCC) of the lung. METHOD: Two SCC cell lines and 4 immortalized bronchial epithelial cell lines (as a precancerous model) were examined by Western blot for TPX2 expression. Reverse transcription-polymerase chain reaction analysis for TPX2 was also performed using tumor tissues from 21 patients with SCC of the lung. The expression of TPX2 was studied by immunohistochemistry (using tissue microarray) on paraffin-embedded sections of pulmonary SCC and corresponding precancerous lesions from a group of 319 patients. RESULTS: TPX2 was variably expressed in all the cell lines studied. Compared with matched controls using normal lung tissue, high level of TPX2 mRNA was detected in 16 of the 21 SCC tumor tissue samples analyzed. Immunohistochemical study showed that TPX2 was mainly present in tumor tissues but not in normal controls. The expression of TPX2 correlated with tumor grade, stage and nodal status. As for precancerous lesions, the level of TPX2 was also increased, in accordance with the degree of dysplasia. CONCLUSIONS: Expression of TPX2 may play a role in carcinogenesis of bronchial epithelium and tumor progression of pulmonary SCC. It may also represent a potential biomarker for surveillance of SCC of lung.


Assuntos
Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/biossíntese , Neoplasias Pulmonares/patologia , Proteínas Associadas aos Microtúbulos/biossíntese , Proteínas Nucleares/biossíntese , Lesões Pré-Cancerosas/patologia , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Nucleares/genética , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise Serial de Tecidos
14.
Lung Cancer ; 54(2): 155-62, 2006 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16938365

RESUMO

BACKGROUND: The E2F3 transcription factor has an established role in controlling cell cycle progression. In previous studies we have provided evidence that nuclear E2F3 overexpression represents a mechanism that drives the development of human bladder cancer and that determines aggressiveness in human prostate cancer. We have proposed a model in which E2F3 overexpression co-operates with removal of the E2F inhibitor pRB to facilitate cancer development. Since small cell lung cancers (SCLC) have one of the highest reported frequencies of functional abnormalities in the pRB protein (90%) of any human cancer, we wish to assess to what extent E2F3 would be overexpressed in this and other classes of human lung cancer. METHODS: Immunohistochemical techniques were used to assess the E2F3 status in 428 samples of lung cancers, lung carcinoids, normal bronchial epithelium and normal lung tissue. RESULTS: E2F3 is overexpressed in 55-70% of squamous cell carcinomas and 79% of adenocarcinomas of the lung. In addition very high level expression of nuclear E2F3 is found in almost all small cell lung cancers analysed. When considered together with published data our observations indicate that co-operation between pRB functional knockouts and E2F3 overexpression may represent a mechanism of development of SCLC.


Assuntos
Adenocarcinoma/metabolismo , Fator de Transcrição E2F3/metabolismo , Neoplasias Pulmonares/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Tumor Carcinoide/genética , Tumor Carcinoide/metabolismo , Tumor Carcinoide/patologia , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Núcleo Celular/metabolismo , Fator de Transcrição E2F3/genética , Regulação Neoplásica da Expressão Gênica , Genes do Retinoblastoma , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Análise de Sequência com Séries de Oligonucleotídeos
15.
Zhonghua Zhong Liu Za Zhi ; 28(10): 750-2, 2006 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-17366786

RESUMO

OBJECTIVE: To investigate expression of serum breast cancer resistance protein (BCRP) in non-small cell lung cancer patient (NSCLC) and healthy adult, and its correlation with chemosensitivity as one passible value of BCRP in clinical application. METHODS: Venous blood specimens of 44 advanced NSCLC patients and 30 healthy adults were collected. Antibody of BCRP was used to detect its expression in the experiment. Part of venous specimens were randomly selected for Western-blot, and all specimens were examined by ELISA at last. Chemotherapy response of these patients was observed in order to analyze the correlation between BCRP expression level and chemosensitivity. RESULTS: Western blot result showed that BCRP expression can be detected both in NSCLC patient and normal adult. The expression level in NSCLC patients detected by ELISA was significantly higher than that in the healthy adults (P = 0.00); which was also significantly higher in chemo-resistant patients than that in the chemosensitive (P = 0.02) and the healthy adults (P = 0.00); however, BCRP expression in chemo-sensitive patients was not significantly different from that in the healthy adults (P = 0.08). CONCLUSION: Breast cancer resistance protein (BCRP) is found to be expressed at high level in the serum of NSCLC patient, the intensity of BCRP expression may be correlated with chemotherapy resistance in NSCLC, and the high level expressing of BCRP may indicate resistance to the platinum-based chemotherapy regimen. Detection of serum BCRP may someday become a useful bio-marker in predicting chemosensitivity of NSCLC.


Assuntos
Transportadores de Cassetes de Ligação de ATP/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Proteínas de Neoplasias/sangue , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Indução de Remissão , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina
16.
Zhonghua Yi Xue Za Zhi ; 86(37): 2611-4, 2006 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-17198586

RESUMO

OBJECTIVE: To investigate the influences of PC cell-derived growth factor (PCDGF) and breast cancer resistance protein (BCRP) on the curative effects of platinum-based chemotherapeutic regimens for advanced non-small cell lung cancer (NSCLC). METHODS: Specimens of cancer were collected from 87 chemotherapy-naive patients with advanced NSCLC, 61 males and 26 females, aged 42 - 75. Immunohistochemistry was used to examine the expression of PCDGF and BCRP. After the collection of pathological specimens the patients underwent platinum-based chemotherapy. The relationship between the expression of PCDGF and BCRP and the curative effects of chemotherapy was analyzed. RESULTS: The overall response rate (OR) to chemotherapy of the 87 patients was 41.38% (36/87), 36 of the patients were chemosensitive (41.38%), and the other 51 were chemoresistant (58.62%). Forty-six of the 87 patients (52.9%) were PCDGF positive, the PCDGF positive rate of the chemoresistant patients was 74.5%, significantly higher than that of the chemosensitive patients (19.4%, P = 0.000). The patients with high PCDGF expression intensity were all chemoresistant. PCDGF expression was significantly associated with response of chemotherapy (P = 0.000). The overall positive BCRP expression rate was 67.82% (59/87). Of the 51 chemoresistant patients 46 were BCRP positive (90.2%), a rate significantly higher than that of the chemosensitive patients (36.1%, P = 0.000). The intensity of BCRP expression was significantly associated with response to chemotherapy (P = 0.000). CONCLUSION: PCDGF and BCRP may be used as biomarkers to predict the first-line response to chemotherapy in patients with advanced NSCLC.


Assuntos
Transportadores de Cassetes de Ligação de ATP/biossíntese , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Neoplasias/biossíntese , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Progranulinas
17.
J Chromatogr B Analyt Technol Biomed Life Sci ; 816(1-2): 145-51, 2005 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-15664344

RESUMO

The p16 tumor suppressor gene is inactivated by promoter region hypermethylation in many types of tumor. Recent studies showed that aberrant methylation of the p16 gene is an early event in many tumors, especially in lung cancer, and may constitute a new biomarker for early detection and monitoring of prevention trials. We detected tumor-associated aberrant hypermethylation of the p16 gene in plasma and tissue DNA from 153 specimens using a modified semi-nested methylation-specific PCR (MSP) combining plastic microchip electrophoresis or slab gel electrophoresis, respectively. Specimens were from 79 lung cancer patients, 15 abdominal tumor patients, 30 positive controls and 30 negative controls. The results showed that the positive rate obtained by microchip electrophoresis was more than 26.6% higher and the same specificity was kept when compared with slab gel electrophoresis. The microchip electrophoresis can rapidly and accurately analyze the PCR products of methylated DNA and obviously improve the positive rate of diagnosis of cancer patients when compared with gel electrophoresis. This method with the high assay sensitivity might be used for detection of methylation of p16 gene and even to facilitate early diagnosis of cancer patients.


Assuntos
Metilação de DNA , Eletroforese em Microchip/métodos , Genes p16 , Neoplasias/genética , Neoplasias Abdominais/sangue , Neoplasias Abdominais/genética , Eletroforese em Microchip/instrumentação , Estudos de Viabilidade , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Polimetil Metacrilato , Sensibilidade e Especificidade
18.
Zhonghua Zhong Liu Za Zhi ; 27(10): 598-601, 2005 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-16438868

RESUMO

OBJECTIVE: To identify prognostic factors in patients with gastrointestinal stromal tumors (GIST). METHODS: Hematoxylin and eosin (H&E) stained histopathological slides of tumors from patients with mesenchymal neoplasms growing in the gastrointestinal tract and abdomen were reviewed. Two histologically representative areas were identified and chosen for tissue microarray. Immunohistochemical staining was performed to demonstrate c-kit protein (CD117), CD34, smooth muscle actin, desmin and S-100 protein. The relations of various clinicopathologic features to outcome were analyzed. RESULTS: The overall disease-specific survival of 194 patients was 93.5% at 1 year, 72.1% at 3 years and 63.2% at 5 years. Univariate analysis indicated that the tumor size, mitotic count, primary location, necrosis, high cellularity, mucosal invasion, mixed cell type, hemorrhage, direct tumor invasion of surrounding tissue, male sex, incompleteness of resection, cytologic atypia were significant predictors of survival. Multivariate analysis showed that tumor size, mitotic count, necrosis, direct tumor invasion of surrounding tissue and male sex were poor prognostic signs. CONCLUSION: Tumor size and mitotic count are important prognostic factors. However, to evaluate the prognosis of these tumors, a surgical pathologist should incorporate multiple parameters into their histologic evaluation in attempt to reach an appropriate opinion on the aggressiveness of GIST.


Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico , Idoso , Feminino , Seguimentos , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Taxa de Sobrevida
19.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 26(5): 543-8, 2004 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-15562769

RESUMO

OBJECTIVE: To establish immortalized cell line from the urothelium of the urinary bladder and identify the characteristics of the cell line. METHODS: Human papillomavirus 16 (HPV-16) plasmid was used to transfect urothelium of infant urinary bladder in vitro with the help of Fugene-6, and this plasmid contained E6 and E7 genes of HPV-16. We also identified the existence of HPV-16 E6 and E7 genes and the biological characteristics of the cell line by PCR, immunohistochemistry, and the biology identification. RESULTS: BLTR-4 cell line, produced from the transfection of HPV-16K plasmid, was a cell line from urothelium with the expression of HPV-16 E6 and E7 genes. It had been cultured more than 70 passages, and the characteristics of growth was similar to the immortalized cell line as reported. CONCLUSIONS: BLTR-4 cell line is an immortalized cell line from urothelium of the urinary bladder, which contains HPV-16 E6 and E7 genes. BLTR-4 cell line is a good experimental model to investigate the relationship of the infection of high risk HPV and transitional cell carcinoma (TCC) in vitro.


Assuntos
Linhagem Celular Transformada , Proteínas Oncogênicas Virais/genética , Papillomaviridae/genética , Proteínas Repressoras/genética , Bexiga Urinária/citologia , Humanos , Proteínas E7 de Papillomavirus , Infecções por Papillomavirus/virologia , Plasmídeos/genética , Transcrição Genética , Transfecção , Infecções Tumorais por Vírus/virologia , Neoplasias da Bexiga Urinária/virologia
20.
Yi Chuan Xue Bao ; 31(4): 389-94, 2004 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-15487509

RESUMO

The investigations on the role of DNA methylation in carcinogenesis have been mainly focused on promoter hypermethylation of tumor suppressor genes. As a number of genes associated with cancer development may be influenced by DNA methylation, identification of these genes is of great importance for understanding the epigenetic alteration in carcinogenesis. In this study, hypermethylated regions of genomic DNA from Chinese lung cancer patients were identified by a modified methylation-sensitive arbitrarily primed PCR (MS-AP-PCR). Eight hypermethylated DNA fragments (HMDF) were separated from a PCR product region between 300 and 500bp in size. After cloning, sequencing and searching with Blast and NewCpGseek programs,the result showed that all of them were typical CpG island sequences, four fragments had 99% approximately 100% homology to regions on human chromosome 2, 7, 9 and 10, respectively,but only one revealed to be known gene. Neural Network Promoter Prediction, TSSG and TSSW programs were run to analyze possible functions of the rest 7 fragments, of which 4 were identified as candidate promoter regions, indicating that they might belong to new genes. The hypermethylated DNA fragments identified in this study might be specific epigenetic alterations in the Chinese lung cancer.


Assuntos
Metilação de DNA , Neoplasias Pulmonares/genética , Idoso , Idoso de 80 Anos ou mais , Ilhas de CpG , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas
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