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1.
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
2.
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
3.
Zhonghua Bing Li Xue Za Zhi ; 39(6): 391-5, 2010 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-21055156

RESUMO

OBJECTIVE: To establish DNA microarrays-based microRNA (miRNA) expression profiles of squamous cell carcinoma of larynx, using archived formalin-fixed paraffin-embedded tissue blocks, and to screen out and identify the differentially expressed miRNAs associated with the biological characteristics of this malignant disease. METHODS: Total RNA was prepared from the formalin-fixed paraffin-embedded tissue blocks. After quality identification and fluorescent labeling, the RNA samples were hybridized with the Agilent human miRNA microarrays which contains 723 probes for human miRNAs. The data was processed with the softwares GeneSpring GX and R-Project. RESULTS: From the formalin-fixed paraffin-embedded tumor blocks collected, 24 RNA samples were obtained with the quality accorded to the requirement of miRNA microarray analysis, and both the hybridization and consequent data processing were accomplished. A total of 319 miRNAs were identified and among them 96 were detected in all the 24 formalin-fixed paraffin-embedded blocks of laryngeal carcinoma; and 5 differentially expressed miRNAs (false discovery rate < 0.05) were found to be associated significantly with the lymphatic metastasis of laryngeal squamous cell carcinoma (P < 0.05), including miR-23a(*), miR-28-5p, miR-15a, miR-16 and miR-425. CONCLUSIONS: Histopathological archives of well-annotated formalin-fixed paraffin-embedded tissue specimens are the valuable resources for miRNA study including to collect RNA samples for miRNA microarray analysis. A panel of differentially expressed miRNAs (miR-23a(*), miR-28-5p, miR-15a, miR-16 and miR-425) derived from the miRNA expression profile may serve as the potential molecular biomarkers for the prediction of metastasis development in laryngeal squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Perfilação da Expressão Gênica , Neoplasias Laríngeas/metabolismo , MicroRNAs/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Metástase Linfática , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Inclusão em Parafina
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 32(4): 389-93, 2010 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-20868595

RESUMO

OBJECTIVE: To explore the association between chromosomal disequilibrium and chemoresistance/chemosensitivity in non-small cell lung cancer (NSCLC) using comparative genomic hybridization (CGH). METHODS: Genomic DNA samples were prepared from the tumor tissues in paraffin-embedded sections derived from 88 patients with advanced NSCLC (18 with chemosensitivity and 16 with chemoresistance). The DNAs were first amplified by a degenerate oligonucleotide prime-polymerase chain reaction protocol and then labeled with fluorescence as probes for CGH analyses. The correlations of the resulting chromosomal imbalances with the chemo-sensitivity and other pathological features of the patients were analyzed. RESULTS: A total of 640 abnormal chromosome regions including 96.12% gains and 3.88% losses were detected in 88 specimens. The results indicated that the most frequently gained chromosome regions were 19p13.1-13.3 (39/88, 44.12%), followed by 9q12-q22 (26/88, 29.41%), 22q12-q13 (26/88, 29.41%), and Xq (29/88, 32.35%). The total number of abnormal regions related with chemo-sensitivity was 188( 182 gains and 6 losses), while the number of the abnormal regions linked to the chemoresistance was 452 (431 gains and 21 losses) (P=0.005). Gains of 14p12-p13 and 19p were significantly correlated with the chemosensitivity of the NSCLC (P=0.006). Gains of 1q12-q22, 10q25-q26, 5p15.1-p15.3, 19q13.2-13.4, 20p11.2-p12, 21q22, and Xp 21-p22.1 were also significantly correlated with the chemoresistance (P]0.005, 0.029, 0.039, 0.029, 0.039, 0.016, and 0.006, respectively). No correlation between the chromosome abnormalities and other clinical features was observed. CONCLUSIONS: The specific gains and losses of chromosome region is correlated with platinum-based first-line chemotherapy in NSCLC patients,as confirmed by CGH detection. This finding is useful for further identifying the chemosensitivity-related functional genes, predicting clinical effectiveness, and achieve individualized treatment in the future.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Hibridização Genômica Comparativa , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Aberrações Cromossômicas , Feminino , Humanos , Cariotipagem , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
Zhonghua Zhong Liu Za Zhi ; 30(8): 616-9, 2008 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-19102942

RESUMO

OBJECTIVE: To evaluate the value of application of cellular protein markers stained by immunocytochemistry in combination with ThinPrep bronchial brush cytology in classification of lung cancer subtypes. METHODS: Remaining bronchial brush cytology samples from 206 lung cancer patients with positive cytological diagnosis and 45 fine needle aspiration samples of resected lung carcinomas were collected. The expressions of CK10/13, CK7, CK18, CD56 and SYN in those samples were detected by immunocytochemistry (ICC) using corresponding antibodies. RESULTS: The sensitivity and specificity of CK10/13 were 94.7% and 72.0%, respectively, in diagnosis of squamous cell carcinoma. The sensitivity and specificity of CK7 were 98.6% and 61.5%, and those of CK18 were 98.6% and 37.5%, respectively, in diagnosis of adenocarcinoma. The sensitivity and specificity of CD56 were 86.3% and 82.9%, and those of SYN were 81.6% and 93.5%, respectively, in diagnosis of small cell lung cancer. No significant difference was found in the expressions of CK10/13, CK7 and CK18 protein markers among differently differentiated lung squamous cell carcinomas and adenocarcinomas (P > 0.05). The classification rate of cytology in combination with ICC in differential diagnosis for 44 cases of unclassified lung cancer reached 90.0% for squamous cell carcinoma, 96.3% for adenocarcinoma, and 100.0% for small cell lung carcinoma. CONCLUSION: Application of cellular protein markers in combination with ThinPrep bronchial brush cytology is helpful to improve the differential diagnosis of lung cancer subtypes, and may become a supplementary diagnostic method in subclassification of lung cancer.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Adenocarcinoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Brônquios/patologia , Broncoscopia , Antígeno CD56/metabolismo , Carcinoma de Células Escamosas/metabolismo , Citodiagnóstico/métodos , Técnicas Citológicas , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Queratina-13/metabolismo , Queratina-18/metabolismo , Queratina-7/metabolismo , Neoplasias Pulmonares/classificação , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Carcinoma de Pequenas Células do Pulmão/metabolismo , Sinaptofisina/metabolismo
6.
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
7.
Zhonghua Wei Chang Wai Ke Za Zhi ; 10(1): 29-32, 2007 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-17253169

RESUMO

OBJECTIVE: To investigate the clinicopathological characteristics and prognostic factors in patients with intra-abdomen extragastrointestinal stromal tumors (EGISTs). METHODS: The data of 47 patients of mesenchymal neoplasms that arose from the abdominal cavity and retroperitoneum, collected from July 1987 to June 2003 in our hospital with complete clinical and pathological data, were investigated retrospectively. EGISTs were diagnosed by reviewing the tumor slides stained with hematoxylin and eosin (H&E). Immunohistochemistry staining were performed on CD117, CD34, smooth muscle actin, Desmin and S-100 proteins. The relations of various clinicopathologic characteristics and outcomes were examined. RESULTS: Among the 47 cases, 30 tumors were confirmed to be EGISTs. Twelve cases arose from the mesentery, six from small omentum, eight from retroperitoneum and four from the abdominal cavity. The size of tumors ranged from 4 to 30 cm (median 12.5 cm) in diameter and the tumor cell components mainly included spindle cells (23 cases), epithelioid cells (4 cases), and mixed cells (3 cases). The follow-up rate was 90% and the median follow up time was 44 months. The patient survival rates at 1, 5 and 10 years were 79.7%, 59.5% and 45.4% respectively. Univariate analysis showed that tumor size >10 cm, tumor necrosis, mitoses > or =5/50HPF, obvious nuclear atypia, moderate and poor differentiated tumor cells were predictors of poor prognosis. CONCLUSIONS: EGISTs have specific clinical behaviors. The parameters used for predicting GISTs prognosis are not completely applicable for EGISTs. Tumor necrosis, obvious nuclear atypia and mitoses > or =5/50HPF help to predict aggressive behaviors in EGISTs.


Assuntos
Neoplasias Peritoneais/patologia , Neoplasias Retroperitoneais/patologia , Adulto , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
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
9.
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
11.
Zhonghua Zhong Liu Za Zhi ; 28(8): 603-5, 2006 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17236555

RESUMO

OBJECTIVE: To investigate the expression of PC cell-derived growth factor (PCDGF) in the serum of non-small cell lung cancer (NSCLC) patients and healthy adults, and it's correlation with chemotherapeutic sensitivity. METHODS: The venous blood samples of 44 advanced NSCLC patients and 30 healthy adults were collected, and PCDGF mono-antibody was used for detection in the experiment. A part of specimens were randomly selected for Western-blot, and all specimens were eventually examined by ELISA. Chemotherapeutic response of these patients was recorded in order to analyze the correlation between PCDGF expression level and chemotherapeutic sensitivity. RESULTS: Western blot results indicated that there was PCDGF expression both in NSCLC patients and healthy adults, and the expressing intensity of PCDGF in NSCLC patients was higher than that in healthy adults. The result of ELISA showed PCDGF expression in the patients whoever was chemoresistant or chemosensitive was significantly higher than that in healthy adults (P < 0.01), However, in chemoresistant patients, it was significantly higher than that in chemosensitive with a borderline statistical difference (P < 0.05). CONCLUSION: PC cell-derived growth factor is found to be not only expressed in healthy adult but also in NSCLC patient at a high level in the serum, which may indicate metastasis and active proliferation in NSCLC. The intensity of PCDGF expression may be correlated with chemotherapy response and the high level expressing of PCDGF may indicate resistant to platinum-based chemotherapeutic regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias Pulmonares/sangue , Adulto , Idoso , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Progranulinas , Indução de Remissão , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina
13.
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
14.
Artigo em Chinês | MEDLINE | ID: mdl-16266515

RESUMO

OBJECTIVE: To study the microsatellite abnormalities of the aromatic amine exposure-associated transitional cell carcinoma (TCC) and sporadic TCC of urinary bladder, and to evaluate the potential of microsatellite analysis on detection of this diseases. METHODS: Based on our previous investigations, 5 microsatellite markers (D17S695, D9S162, D3S1295, DBH and D3S1234) that had high frequencies of loss of heterozygosity (LOH) in sporadic TCC, were selected for analysis with the bladder lesions derived from 16 patients with aromatic amine exposure history. The microsatellite analysis with urine sediments from the post-operated patients was also carried out. RESULTS: There was at least one informative marker out of the 5 microsatellite foci showed polymorphism in the DNA derived from 16 patients examined. Within 87.50% (14/16) patients, LOH was detected in the bladder lesions at least with one microsatellite marker. The LOH frequency of D3S1295 was higher in occupational TCC patients than that in sporadic TCC patients. The diagnostic accordance rate of patients showed LOH in at least one microsatellite marker with patients diagnosed by pathology was 81.25% (13/16). In the urine sediments from 8 TCC post-operated patients, LOH was found at least with one microsatellite marker. CONCLUSION: There could be a different LOH pattern in aromatic amine exposure-associated TCC, and genes near D3S1295 might play a role in the occupational exposure-associated TCC.


Assuntos
Carcinoma de Células de Transição/patologia , Hidrocarbonetos Aromáticos/toxicidade , Repetições de Microssatélites , Exposição Ocupacional , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/genética , Humanos , Neoplasias da Bexiga Urinária/genética
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 8(3): 213-6, 2005 May.
Artigo em Chinês | MEDLINE | ID: mdl-16167230

RESUMO

OBJECTIVE: To explore the prognostic factors in patients with gastrointestinal stromal tumors of the small intestine. METHODS: Tumor slides stained with hematoxylin and eosin from these patients were reviewed. Two histomorphologically representative areas were identified and arrayed on a tissue microarray. Immunohistochemistry staining were performed using antibodies to detect the expression of c-kit protein (CD117), CD34, smooth muscle actin, desmin, S-100, Ki-67, P53 and bcl-2 protein. The relationship between clinicopathologic features and prognosis was analyzed by univariate analysis. RESULTS: The 1-, 3-, 5-year survival rate of 58 such patients were 98.3%, 69.7%, and 50.9% respectively. The prognosis was related with tumor size and gender by univariate analysis (P< 0.05). CONCLUSION: More attention should be paid to the male patients with small intestine stromal tumors,especially those with tumors size> 5 cm, because those tumors are more likely to metastasize than smaller tumors (< or = 5 cm).


Assuntos
Tumores do Estroma Gastrointestinal/patologia , Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Adulto , Idoso , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Humanos , Imuno-Histoquímica , Neoplasias Intestinais/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico
16.
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
17.
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
18.
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
19.
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
20.
Chin Med J (Engl) ; 117(10): 1485-8, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15498370

RESUMO

BACKGROUND: Recent studies suggest that circulating DNA may be a potential tumor marker for lung cancer, but most of these studies are conducted between healthy controls and lung cancer patients, with few or no benign lung disease patients included. The objective of this study was to evaluate the performance of plasma DNA quantification in discriminating lung cancer from the healthy and benign lung disease. METHODS: Plasma DNA was extracted with a QIAamp DNA Blood Midi kit and quantified by a PicoGreen dsDNA quantitation kit in 44 healthy individuals, 36 benign lung disease patients and 67 lung cancer patients. Discrimination power was evaluated by the receiver operating characteristic curve. RESULTS: Plasma DNA values were significantly increased in lung cancer patients, especially in those with metastases, and in benign lung disease patients compared with that in the healthy individuals (P < 0.001, respectively). The values in lung cancer patients were significantly increased compared with that in the benign lung disease patients (P < 0.001). The area under the curve was 0.96 [95% confidence interval (CI) 0.92 - 0.99] for the healthy versus lung cancer, 0.73 (95% CI 0.64 - 0.83) for lung cancer versus benign lung disease, and 0.86 (95% CI 0.80 - 0.91) for lung cancer versus the healthy and benign lung disease. CONCLUSIONS: Plasma DNA quantification has a strong power to discriminate lung cancer from the healthy and from the healthy and benign lung disease, less power to discriminate lung cancer from benign lung disease. Plasma DNA quantification may be useful as a screening tool for lung cancer.


Assuntos
DNA/sangue , Neoplasias Pulmonares/diagnóstico , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias
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