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2.
Zhonghua Bing Li Xue Za Zhi ; 47(10): 775-779, 2018 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-30317733

RESUMO

Objective: To compare different specimen types of lung adenocarcinoma in the detection of epidermal growth factor receptor (EGFR) gene and to correlate EGFR mutations with patient clinical features. Methods: One hundred lung adenocarcinoma cases were collected from June to December in 2015, at the First Affiliated Hospital of Xinjiang Medical University.Of the 100 lung adenocarcinoma samples, 43 were male and 57 were female. The age was from 40 to 88 years old, and the average age was 66 years. One hundred lung adenocarcinoma cases were divided equally into two groups. Mutation analysis of EGFR gene by real-time PCR was performed using biopsied tissue and paired blood samples in one group (n=50) and using pleural effusion and paired blood samples in the other group (n=50). Results: The mutation rate of EGFR gene in biopsy samples was 54% (27/50) , higher than that of blood samples (46%, 23/50), but without statistical differences (χ(2)=0.640, P=0.424). In contrast, mutation rate of EGFR gene in pleural effusion samples (42%, 21/50) was higher than that of blood samples (34%, 17/50), but without statistical differences(χ(2)=0.679, P=0.409). Two patients had EGFR mutation detected in paired blood samples but not in the corresponding biopsy samples, and four patients had EGFR mutation detected in pleural effusion samples but not in their paired blood samples. The mean progression-free survival of patients with detectable EGFR mutation were 9.5 months (tissue samples), 8.6 months (pleural effusion) and 8.5 months (blood). However, there was no statistical difference. Conclusions: Blood samples may be used to assess EGFR mutations for patients with lung adenocarcinoma. However, further studies are needed to improve the sensitivity and accuracy in the detection of EGFR mutations using blood samples.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Análise Mutacional de DNA , Receptores ErbB , Feminino , Genes erbB-1 , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Pleura , Derrame Pleural
3.
Zhonghua Bing Li Xue Za Zhi ; 47(7): 492-498, 2018 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-29996312

RESUMO

Objective: To study the associations between variants of mTORC1 of PI3K/AKT/mTOR pathway and colorectal cancer. Methods: In this hospital-based case-control study, at the First Affiliated Hospital, Xinjiang Medical University from 2000 to 2013, 665 primary colorectal cancer cases and 695 cancer-free controls were genotyped at 10 potentially functional single nucleotide polymorphism (SNPs) loci of mTORC1 (mTOR: rs1034528, rs2295080; Raptor: rs1062935, rs3751934; mLST8: rs3160, rs26865; DEPTOR: rs2271900, rs4871827; AKT1S1: rs2290774, rs2353005) to assess their associations with risk of colorectal cancer by Logistic regression analysis. Results: In single-locus analysis, found a significantly decreased risk of colorectal cancer associated with mLST8 rs26865 by recessive genetic model, especially in populations of ≤68 years of age (OR=0.64; 95%CI=0.43-0.96, P=0.031), female (OR=0.61; 95%CI=0.38-0.99, P=0.046), non-smoking (OR=0.55; 95%CI=0.35-0.87, P=0.010). mTOR rs1034528 CC genotypes were associated with higher risk of colorectal cancer in >68-year-old populations (OR=3.34; 95%CI=1.12-9.91, P=0.030). Raptor rs3751934 CA/AA genotypes were associated with lower colorectal cancer risk in population of body mass index(BMI)>25 kg/m(2) (OR=0.68; 95%CI=0.47-0.98, P=0.038); and AKT1S1 rs2290774 CC genotypes were associated with lower colorectal cancer risk in non-smoking population (OR=0.67; 95%CI=0.45-0.99, P=0.048). Furthermore, found that populations carrying more than two low-risk genotypes were associated with lower colorectal cancer risk, compared with that of populations carrying less than two low-risk genotypes (OR=0.74, 95%CI=0.58-0.95, P=0.017), especially in population of ≤68 years of age, male and BMI>25 kg/m(2,) and non-smoking. Conclusions: SNPs of mTORC1-related genes individually or jointly contribute to colorectal cancer susceptibility in Chinese. Further studies of larger cohorts are needed to validate the findings.


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/etnologia , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China , Neoplasias Colorretais/etnologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Análise de Regressão , Proteína Regulatória Associada a mTOR/genética , Medição de Risco , Serina-Treonina Quinases TOR/genética
5.
Zhonghua Bing Li Xue Za Zhi ; 47(1): 25-31, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29325247

RESUMO

Objective: To investigate the role of PRDM1 gene inactivaion in the regulation of C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of its immunophenotype and prognosis. Methods: 100 cases paraffin-embedded DLBCL tissues were collected from January 2009 to December 2015 at the First Affiliated Hospital of Xinjiang Medical University along with 20 cases of reactive proliferative lymph nodes as control. Immunohistochemical methods were used to detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and PAX5 protein. The tumors were classified into two subtypes according to Hans classification.The expression of PRDM1 and C-MYC gene in tumor group and control group was detected by reverse transcription PCR (RT-PCR) and the relationship between PRDM1 and C-MYC gene was analyzed.OCI-LY1 (GCB subtype) and OCI-LY3 (non-GCB subtype) cell lines were transfected with small interfering RNA by cationic liposome reagent transfection, and the expression of C-MYC in the transfected cell lines was detected by RT-PCR and Western blot. The Kaplan-Meier method was used to analyze the prognostic significance of PRDM1/Blimp1 and C-MYC at protein and mRNA levels. Results: There were 27 cases of GCB subtype and 73 cases of non-GCB subtype according to Hans classification. The positive expression of Blimp1 in DLBCL group and proliferative lymph nodes in control group was seen in 26(26.0%) and 20 cases(100%), respectively. There were 58 cases with high expression of PRDM1 at mRNA level, including 22 cases of GCB subtype and 36 cases non-GCB subtype, and the difference was statistically significant (P=0.004). There were differences in PRDM1 gene expression between the two immunological subtypes, serum lactate dehydrogenase (serum LDH) level, presence of B symptoms, tumor primary sites and other clinical pathological parameters, while C-MYC expression was different in gender, IPI score, and serum LDH levels. Upon PRDM1/Blimp1 gene silencing in the two cell lines, C-MYC protein and gene expression were up-regulated in the transfection group, compared with the blank control group and negative control group by reverse transcription PCR and Western blot analyses. Moreover, PRDM1 expression was significantly associated with C-MYC(χ(2)=7.648, P=0.006) at mRNA level. Conclusion: The up-regulation of C-MYC gene expression induced by PRDM1 inactivation in DLBCL may play an important role for the development of DLBCL.PRDM1 protein and mRNA are associated with immunophenotyping and PRDM1 mRNA is a marker of poor prognosis.


Assuntos
Inativação Gênica , Genes myc , Linfoma Difuso de Grandes Células B/genética , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Antígenos CD20/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Imunofenotipagem , Linfonodos/patologia , Linfoma Difuso de Grandes Células B/patologia , Fator de Transcrição PAX5/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/metabolismo , Proteínas Repressoras/metabolismo , Regulação para Cima
6.
Zhonghua Bing Li Xue Za Zhi ; 46(5): 309-313, 2017 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-28468035

RESUMO

Objective: To investigate the point mutation of epidermal growth factor receptor (EGFR) gene and clinicopathologic characteristics in patients with non-small cell lung cancers(NSCLC)of Xinjiang region. Methods: Five-hundred and eighty-two cases of paraffin-embedded tissue in patients with NSCLC were collected between January 2013 and December 2015 in the First Affiliated Hospital of Xinjiang Medical University. The DNA was extracted from these tissues by Qiagen kit, to test thirty-two mutations in EGFR exons 18, 19, 20 and 21 using fluorescent quantitative qRT-PCR technology by TaqMan probe; the clinicopathologic features of patients were analyzed according to the mutation status of EGFR. Results: There were 173 cases with EGFR gene mutation in 582 cases of paraffin-embedded tissue in patients with NSCLC, and the mutation rate was 29.7%(173/582). There were statistical difference in female patients (50.5%, 98/194), no history of smoking(47.3%, 96/203), high differentiation(6/9), adenosquamous carcinoma(6/11), peripheral location (34.9%, 88/252), and surgical specimens(38.2%, 83/217), respectively (P<0.05). Multiple factors Logistic analysis showed that gender, degree of differentiation, and pathologic types had statistical differences to EGFR when α=0.05. There were no statistical differences between other variants. Conclusions: There are higher rate EGFR gene mutation in women patients, non-smokers, and well-differentiated, adenocarcinoma. Gender, degree of differentiation and pathological patterns are independent influencing factors on EGFR mutation status.


Assuntos
Adenocarcinoma/genética , Carcinoma Adenoescamoso/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Éxons , Genes erbB-1 , Neoplasias Pulmonares/genética , Mutação Puntual , Adenocarcinoma/patologia , Carcinoma Adenoescamoso/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , China , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Taxa de Mutação , Fatores Sexuais , Fumar
7.
J Hum Hypertens ; 31(6): 388-394, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28054570

RESUMO

This study investigates socioeconomic differences in prevalence, awareness, control and self-management of hypertension in rural China. A cross-sectional survey was conducted among four ethnic minority groups in Yunnan Province: Na Xi, Li Shu, Dai and Jing Po. Approximately 5532 consenting individuals aged ⩾35 years (48.4% of whom were male) were selected to participate in the study using a stratified, multistage sampling technique. Information about participants' demographic characteristics and hypertension awareness, treatment, control and self-management practices was obtained using a standard questionnaire. The age-standardised prevalence of hypertension in the study population was 33.6%. In hypertensive subjects, the overall levels of awareness, treatment and control of hypertension were 42.1%, 28.5% and 6.7%, respectively. Approximately 58.7% of hypertensive patients regularly self-monitored blood pressure (BP), 64.7% adhered to their physician-prescribed anti-hypertensive drugs, and 88.0% took at least one measure to control BP. Hypertensive patients of Jing Po ethnicity had the lowest rates of awareness, treatment, control and self-management of hypertension among the four ethnic minority groups studied. Individuals with lower levels of education were more likely to be hypertensive. Further, individuals with lower levels of education had a lower probability of awareness of their hypertensive status and of treatment with antihypertensive medication. Access to medical services was positively associated with awareness of suffering from hypertension, being treated with antihypertensive medication, and compliance with antihypertensive drug treatment. This study suggests that effective strategies to enhance awareness, treatment and management of hypertension should focus on individuals with low levels of education and poor access to medical services.


Assuntos
Anti-Hipertensivos/uso terapêutico , Grupo com Ancestrais do Continente Asiático/psicologia , Conscientização , Pressão Sanguínea/efeitos dos fármacos , Comportamentos Relacionados com a Saúde/etnologia , Hipertensão/tratamento farmacológico , Hipertensão/etnologia , Grupos Minoritários/psicologia , Saúde das Minorias , Saúde da População Rural , Autocuidado , Fatores Socioeconômicos , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Escolaridade , Feminino , Pesquisas sobre Serviços de Saúde , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Acesso aos Serviços de Saúde , Disparidades em Assistência à Saúde/etnologia , Humanos , Hipertensão/fisiopatologia , Hipertensão/psicologia , Masculino , Adesão à Medicação/etnologia , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Prevalência , Resultado do Tratamento
8.
Zhonghua Bing Li Xue Za Zhi ; 45(11): 762-768, 2016 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-27821230

RESUMO

Objective: To investigate clinicopathologic characteristics, immunophenotype and EB virus-related molecular genetic alterations in primary central nervous system diffuse large B cell lymphoma (DLBCL) along with correlation with clinical prognosis. Methods: A total of 30 cases of primary central nervous system DLBCL were retrospectively studied by retrieving clinical data, histological evaluation and immunophenotyping by EnVision two steps methods. The expression of EBER mRNA was detected by in situ hybridization and bcl-2, bcl-6 and C-MYC gene abnormalities were analyzed by interphase fluorescence in situ hybridization. Results: The cases included 18 males and 12 females (sex ratio of 1.5∶1.0) with an age ranging from 24 to 78 years (average age of 52 years, the median age of 53 years). The single primary clinical presentation was focal neurologic deficits. Tumor locations were supratentorial (21 cases), subtentorial (7 cases), involving both locations in 2 cases. Diffuse growth pattern was observed with large lymphoid cells mostly resembling centroblasts with abundant basophilic cytoplasm with oval to round, vesicular nuclei containing fine chromatin. An angiocentric and angiodestructive growth pattern was also present. Other features included perivascular space invasion. Immunohistochemical staining using a panel of CD10, bcl-6 and MUM1, six cases were germinal center-like (GCB) and 24 cases were non-germinal central-like (non-GCB). The positive rates of bcl-2, bcl-6 and C-MYC were 53.3% (16/30), 80.0% (24/30) and 20.0% (6/30), respectively. Genetic alterations were detected by FISH and the gene arrangement rates of bcl-2, bcl-6 and C-MYC were 3.3% (1/30), 16.7% (5/30) and 3.3% (1/30), respectively. There were 19 cases in stage 0-1 disease and 11 cases had stage 2-3 disease. Postoperative follow-up for average 13.6 months showed the median survival of 10 months, one-year survival of 46.7% and 16 patients died within a year. Conclusions: The clinical prognosis of primary central nerve system DLBCL depends on age, clinical performence status score, IPI score, immune classification and treatment. Patients typically progress rapidly with the high mortality within one year of diagnosis. Surgical resection combined with high-dose methotrexate or cytarabine chemotherapy offer the best treatment option.


Assuntos
Neoplasias do Sistema Nervoso Central/patologia , Linfoma Difuso de Grandes Células B/patologia , Adulto , Idoso , Linfócitos B , Neoplasias do Sistema Nervoso Central/química , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/virologia , Feminino , Genes myc , Centro Germinativo , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-6/análise , RNA Viral/análise , Estudos Retrospectivos
9.
Zhonghua Bing Li Xue Za Zhi ; 45(7): 451-6, 2016 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-27430689

RESUMO

OBJECTIVE: To study the associations between genetic variations of Vav3 gene and prostate cancer susceptibility. METHODS: Data were collected in a hospital-based and case-control study of 1 015 prostate cancer cases and 1 068 cancer-free controls collecting from a period of time between 2008 and 2012. Based on the online database, NCBI dbSNP (http: //www.ncbi.nlm.nih.gov/projects/SNP) and SNPinfo (http: //snpinfo.niehs.nih.gov/snpfunc.htm). Functional single nucleotide polymorphisms (SNPs) of Vav3 were screened and genotyped, and assessed their associations with risk of prostate cancer by using logistic regression analysis. Furthermore, the associations between SNPs of Vav3 and some clinicopathological parameters were evaluated. RESULTS: Among the two SNPs investigated, only Vav3 rs12410676 G>A was associated with decreased prostate cancer risk [additive model, OR=0.80 (0.69-0.93), P=0.003; dominant model, OR=0.81 (0.68-0.97), P=0.022; recessive model, OR=0.54 (0.36-0.82), P=0.004]. The combined effect of Vav3 rs8676 G>A and rs12410676 G>A was found as a decreased prostate cancer risk along with the increased variant alleles (P<0.05). Specifically, participants carrying Vav3 rs12410676 AA/AG genotypes were more likely to be at lower prostate cancer risk, compared with participants carrying GG genotypes, in groups of BMI≤25 kg/m(2,) smoking, Gleason>7(4+ 3), and higher invasive prostate cancer. Finally, some positive findings were evidently significant with false positive report probability values at different prior probability levels (0.25, 0.1 and 0.01). CONCLUSION: Vav3 SNPs may contribute to the risk of prostate cancer in Eastern Chinese men, but the effect is weak and needs further validation by larger, multicenter and ethnic-based studies.


Assuntos
Predisposição Genética para Doença , Neoplasias da Próstata/genética , Proteínas Proto-Oncogênicas c-vav/genética , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China/etnologia , Variação Genética , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia
10.
Zhonghua Bing Li Xue Za Zhi ; 45(12): 831-837, 2016 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-28056297

RESUMO

Objective: To investigate PRDM1 gene methylation status, immune classification and their prognostic significance in diffuse large B cell lymphoma (DLBCL). Methods: Immunohistochemical (IHC) staining for CD20, CD10, bcl-2, bcl-6, PRDM1/Blimp-1 and MUM1 was carried out in 100 cases of DLBCL specimens and 20 reactive lymphoid proliferation samples. All patients were classified into germinal center B cell-like (GCB) and activated B cell-like (ABC) subtype according to Hans' algorithmin. PRDM1 gene methylation was detected by methylation-specific PCR (MSP) and its relationship with clinicopathologic parameters was analyzed. OCI-Ly1 (GCB type) and OCI-Ly3 (ABC type) cell lines were transfected by Small interfering RNA(siRNA) with cationic lipid reagent transfection mediated, and the PRDM1/Blimp-1 expression in before and after transfected cell lines were detected with reverse transcription-PCR and Western blot methods. The relationship between PRDM1 gene methylation, clinicopathologic parameter and survival was analyzed using one-way analysis of variance. Results: One hundred patients were classified into 73 (73%) cases of GCB subtypes and 27 (27%) cases of ABC. PRDM1/Blimp-1 was expressed in 21 DLBCL and highly expressed in 20 reactive lymphoid proliferation. PRDM1 gene methylation was detected in 23% (23/100) of DLBCL, while no methylation was detected in all 20 reactive lymphoid proliferation. The difference of the PRDM1 methylation status between DLBCL and the control samples was statistically significant (P=0.004). However, there was no significant correlation between the PRDM1 gene methylation and clinicopathologic parameters (P>0.05). Reverse transcription-PCR and Western blot showed that PRDM1 gene expression was reduced in siRNA-induced group compared with blank control group and negative control group. One-way analysis of variance revealed that aged ≥60 years, performance status score above 3, and the presence of general symptoms were associated with significantly lower overall survival rate. Conclusions: PRDM1 gene silencing with aberrant CpG methylation is probably one of the critical events in the oncogenesis of DLBCL. This may have important implications as a candidate marker for diagnosis and targeted gene therapy. Meanwhile in vitro siRNA transfected OCI-Ly1 and OCI-Ly3 cell lines confirm that PRDM1 gene is a suppressor gene in DLBCL and may represent a novel therapeutic target.


Assuntos
Linfoma Difuso de Grandes Células B/genética , Regiões Promotoras Genéticas , Proteínas Repressoras/genética , Análise de Variância , Antígenos CD20/metabolismo , Linfócitos B , Metilação de DNA , Feminino , Inativação Gênica , Centro Germinativo , Humanos , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Neprilisina/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Proteínas Repressoras/metabolismo , Taxa de Sobrevida , Fatores de Transcrição
11.
Biopolymers ; 29(1): 225-35, 1990 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2328288

RESUMO

We report the application of a new conformation searching algorithm called simulated annealing to the location of the global minimum energy conformation of peptides. Simulated annealing is a Metropolis Monte Carlo approach to conformation generation in which both the energy and temperature dependence of the Boltzmann distribution guides the search for the global minimum. Both uphill and downhill moves are possible, which allows the molecule to escape from local minima. Applications to the 20 natural amino acid "dipeptide models" as well as to polyalanines up to Ala80 are very successful in finding the lowest energy conformation. A history file of the simulated annealing process allows reconstruction and examination of the random walk around conformation space. A separate program, Conf-Gen, reads the history file and extracts all low-energy conformations visited during the run.


Assuntos
Algoritmos , Peptídeos , Fenômenos Químicos , Físico-Química , Dipeptídeos , Método de Monte Carlo , Conformação Proteica , Temperatura
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