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Article in Chinese | WPRIM | ID: wpr-927870


Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(r=0.234,P=0.023),palmoplantar keratoderma(r=0.325,P=0.001),webbing/pseudoainhum(r=0.247,P=0.016),dysphagia(r=0.333,P=0.001),urethral stricture(r=0.280,P=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(χ2=11.292,P=0.001)and anal stenosis(χ2=4.014,P=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).

Adolescent , Adult , Ainhum , Blister , Carcinoma, Squamous Cell , Child , Constriction, Pathologic , Deglutition Disorders/complications , Epidermolysis Bullosa , Female , Humans , Inflammation , Keratoderma, Palmoplantar/complications , Male , Membrane Proteins , Mutation , Neoplasm Proteins/genetics , Periodontal Diseases , Photosensitivity Disorders , Urethral Stricture/complications , Young Adult
Braz. dent. j ; 32(2): 14-26, Mar.-Apr. 2021. tab
Article in English | LILACS, BBO | ID: biblio-1339330


Abstract The study investigated the relationship between genetic polymorphisms and the development of oral mucositis in pediatric patients undergoing chemotherapy involving methotrexate. A longitudinal study was conducted with 64 patients, and oral mucositis was evaluated by the modified Oral Assessment Guide, which aims to diagnose and classify oral mucositis. Epithelial cells were obtained by mouthwash and DNA was extracted. The polymorphisms MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) and ABCG2 (rs2231142) were analyzed by PCR-RFLP method. Demographic, hematological and biochemical data were collected from medical records. Statistical analysis was performed using the SPSS software adopting a p-value of 0.05. Male sex predominated (56.2%), and the mean age was 10.8 years (± 4.9). Oral mucositis affected 65.6% of the patients, of which 61.9% developed the severe form of the disease. For the ABCG2 gene (rs2231142), the rare A allele and CA genotype were more frequent in individuals with mucositis (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). The severity of the disease was mainly observed in younger patients (median = 9 years; p=0.02). Patients with severe oral mucositis presented lower leukocytes count (median = 2.150 mm3) compared to patients with the mild/moderate form (median = 4.200 mm3; p=0.03). Female patients and each 10,000-platelet increase were protective factors against the onset of oral mucositis (p=0.02). It is concluded that rs2231142 polymorphism increases the likelihood of oral mucositis and younger patients and patients with low leukocytes counts are more likely to develop severe form.

Resumo O presente estudo investigou a relação entre cinco polimorfismos genéticos e o desenvolvimento de mucosite oral em pacientes pediátricos recebendo quimioterapia com metrotexato. O estudo longitudinal foi conduzido com 64 pacientes e a mucosite oral avaliada pelo Oral Assessment Guide modificado, que tem como objetivo diagnosticar e classificar a mucosite oral. Células epiteliais bucais foram obtidas por bochecho e o DNA foi extraído. Os polimorfismos MTHFR (rs1801133), DNMT3B (rs2424913), ABCC2 (rs717620), ABCG2 (rs2231137) e ABCG2 (rs2231142), foram analisados pela técnica de PCR-RFLP. Dados demográficos, hematológicos e bioquímicos foram coletados a partir de registros médicos. Análise estatística foi realizada utilizando o software SPSS adotando um valor de p=0,05. Observou-se que, o sexo masculino foi predominante (56,2%), e a idade média foi de 10,8 anos (± 4.9). A mucosite oral acometeu 65,6% dos pacientes, dos quais, 61,9% desenvolveram a forma grave da doença. Para o gene ABCG2 (rs2231142), o alelo raro A e o genótipo CA foram mais frequentes em indivíduos com mucosite (p= 0.02; RR = 0.60; CI = 0.387 - 0.813). A gravidade da doença foi observada principalmente em pacientes mais jovens (mediana = 9 anos; p=0.02). Além disso, os pacientes com mucosite oral grave apresentaram menor contagem de leucócitos (mediana = 2150 mm3) em comparação aos pacientes com a forma leve/moderada (mediana = 4200 mm3; p=0.03). Pacientes do sexo feminino e aumento a cada 10.000 plaquetas foram fatores de proteção contra o aparecimento de mucosite oral (p=0.02). Concluiu-se que a presença do polimorfismo rs2231142 aumenta o risco de o paciente desenvolver a mucosite oral, bem como pacientes mais jovens e menor contagem de leucócitos contribui com a severidade.

Humans , Male , Female , Child , Adolescent , Stomatitis/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , Polymorphism, Genetic , Longitudinal Studies , Leukocyte Count , Neoplasm Proteins/genetics
Article in Chinese | WPRIM | ID: wpr-921956


OBJECTIVE@#To explore the genotype-phenotype correlation in a child with Kabuki syndrome type 1 (KS1) caused by a mosaic frameshift variant of KMT2D gene.@*METHODS@#Trio-based whole exome sequencing (WES) was carried for the patient and her parents. Candidate variant was verified by Sanger sequencing.@*RESULTS@#The proband, a 3-year-and-2-month-old Chinese girl, presented with distinctive facial features, cognitive impairment, mild developmental delay, dermatoglyphic abnormalities, minor skeletal anomalies, ventricular septal defect, and autistic behavior. Trio-based WES revealed that the proband has carried a de novo mosaic frameshit variant of the KMT2D gene, namely NM_003482.3:c.13058delG (p.Pro4353Argfs*31) (GRCh37/hg19), for which the mosaicism rate was close to 21%. The variant was unreported previously and was confirmed by Sanger sequencing. Chromosomal microarray analysis (CMA) has revealed no pathogenic or likely pathogenic copy number variations. Compared with previously reported cases, our patient has presented obvious behavior anomalies including autism, anxiety and sleep problems, which were rarely reported.@*CONCLUSION@#This study has expanded the spectrum of KMT2D gene variants, enriched the clinical phenotypes of KS1, and facilitated genetic counseling for the family.

Abnormalities, Multiple , China , DNA Copy Number Variations , DNA-Binding Proteins/genetics , Face/abnormalities , Female , Hematologic Diseases , Humans , Infant , Neoplasm Proteins/genetics , Phenotype , Vestibular Diseases
Article in Chinese | WPRIM | ID: wpr-888374


OBJECTIVE@#To explore the genetic basis of a child with recurrent infection, multiple malformation and dysmorphism.@*METHODS@#The child and his parents were subjected to trio whole exome sequencing.@*RESULTS@#The child had a complaint of fever and cough, with long and thin eye fissures and long eyelashes. Genetic testing revealed that the child has carried a non-triplet deletion of the KDM6A gene, which was unreported previously. The variant resulted in frameshift and premature termination of the translation. His parents were both of the wild type for the locus. After antibiotic and immunoglobulin treatment, the severe secondary pneumonia caused by immunodeficiency has improved.@*CONCLUSION@#With combined laboratory test, imaging examination and genetic testing, the child was ultimately diagnosed with Kabuki syndrome type 2. The characteristics of immunodeficiency of Kabuki syndrome may render conventional antibiotic treatment ineffective, which deserves clinical attention.

Abnormalities, Multiple , Child , DNA-Binding Proteins/genetics , Face/abnormalities , Genetic Testing , Hematologic Diseases , Histone Demethylases/genetics , Humans , Neoplasm Proteins/genetics , Nuclear Proteins/genetics , Phenotype , Pneumonia , Vestibular Diseases
Article in Chinese | WPRIM | ID: wpr-878716


Objective To investigate the expression of Cripto-1 in pancreatic cancer and to analyze its clinical significance. Methods Cripto-1 expression in normal pancreas,pancreatic cancer and adjacent non-tumor tissues,chronic pancreatitis tissues and other related tissues was evaluated using immunohistochemistry.The association of Cripto-1 expression with the clinicopathological characteristics and the prognostic value of Cripto-1 in patients with pancreatic cancer were analyzed. Results The expression of Cripto-1 was higher in chronic pancreatitis tissues,pancreatic cancer and its metastases than in normal pancreas(P=0.019,P=0.025,and P=0.018,respectively).Cripto-1 overexpression was correlated with poorly differentiated pancreatic cancer.The patients with Cripto-1 upregulation had shorter median survival time(8 months vs.16 months,χ

Biomarkers, Tumor , Carcinoma, Pancreatic Ductal , GPI-Linked Proteins , Humans , Intercellular Signaling Peptides and Proteins , Neoplasm Proteins/genetics , Pancreatic Neoplasms , Prognosis
Rev. bras. ginecol. obstet ; 42(3): 146-151, Mar. 2020. tab
Article in English | LILACS | ID: biblio-1098859


Abstract Objective To investigate the association between genetic polymorphisms in candidate genes or candidate regions and the development of endometriosis in Brazilian women. Methods A total of 30 women between 25 and 64 years old with a diagnosis of endometriosis participated in the present study, as well as 30 matched control women from the same age group, asymptomatic and without family history of the disease. The patients genotypic and allelic frequencies of polymorphisms in the GREB1 gene (rs13394619) and in the intergenic region at position 7p15.2 (rs12700667) were analyzed and compared. Results There was no significant difference in the frequency of genotypes for the A > G polymorphism (rs13394619) in the GREB1 gene between the two groups. However, the distribution frequencies of the genotypes for the A > G polymorphism (rs12700667) in an intergenic region on chromosome 7 were different for control patients and for patients with endometriosis, with higher frequency of the AG genotype compared to the GG between patients with the disease (odds ratio [OR] = 3.49; confidence interval [CI] = 1.47-8.26). Conclusion The present study suggests that the polymorphism in the intergenic region of chromosome 7 is associated with the risk of developing endometriosis in a population of Brazilian women from Juiz de Fora.

Resumo Objetivo Investigar a associação de polimorfismos genéticos em genes candidatos ou regiões candidatas com o desenvolvimento da endometriose em mulheres brasileiras. Métodos Um total de 30 mulheres com diagnóstico de endometriose, com idade entre 25 e 64 anos, participaram da presente pesquisa, bem como 30 mulheres controle, na mesma faixa etária, assintomáticas e sem história familiar da doença. Foram analisadas e comparadas as frequências genotípicas e alélicas de polimorfismos no gene GREB1 (rs13394619) e na região intergênica na posição 7p15.2 (rs12700667) nessas pacientes. Resultados Não houve diferença significativa na frequência dos genótipos para o polimorfismo A > G (rs13394619) no gene GREB1 entre os dois grupos. No entanto, as frequências de distribuição dos genótipos para o polimorfismo A > G (rs12700667) em uma região intergênica no cromossomo 7 foram diferentes entre as pacientes controle e com endometriose, com frequência mais alta do genótipo AG comparado ao GG entre as pacientes com a doença (odds ratio [OR] = 3,49; intervalo de confiança [IC] 95% = 1,47-8,26). Conclusão O presente estudo sugere que o polimorfismo na região intergênica do cromossomo 7 foi associado com o risco do desenvolvimento de endometriose em uma população de mulheres de Juiz de Fora.

Humans , Female , Adult , Genetic Predisposition to Disease , Endometriosis/genetics , Neoplasm Proteins/genetics , Brazil , Case-Control Studies , Polymorphism, Single Nucleotide , Whites , Middle Aged
Rev. bras. ginecol. obstet ; 40(10): 606-613, Oct. 2018. graf
Article in English | LILACS | ID: biblio-977778


Abstract Objective The aim of the present study was to analyze the expression of the CD63, S100A6, and GNB2L1genes, which participate in mechanisms related to the complex pathophysiology of endometriosis. Methods A case-control study was conducted with 40 women who were diagnosed with endometriosis, and 15 fertile and healthy women. Paired samples of eutopic endometrium and endometriotic lesions (peritoneal and ovarian endometriotic implants) were obtained from the women with endometriosis in the proliferative (n = 20) or secretory phases (n = 20) of the menstrual cycle. As controls, paired endometrial biopsy samples were collected from the healthy women in the proliferative (n = 15) and secretory (n = 15) phases of the samemenstrual cycle.We analyzed the expression levels of the CD63, S100A6, and GNB2L1 genes by real-time polymerase chain reaction. Results An increase in CD63, S100A6, and GNB2L1 gene transcript levels was observed in the ectopic implants compared with the eutopic endometrium of the women with and without endometriosis, regardless of the phase of the menstrual cycle. Conclusion These findings suggest that the CD63, S100A6, and GNB2L1 genesmay be involved in the pathogenesis of endometriosis, since they participate in mechanisms such as inhibition of apoptosis, angiogenesis and cell proliferation, which lead to the loss of cell homeostasis in the ectopic endometrium, thus contributing to the implantation and survival of the tissue in the extrauterine environment.

Resumo Objetivo O objetivo do presente estudo foi analisar a expressão dos genes CD63, S100A6 e GNB2L1, que participam em mecanismos relacionados à complexa fisiopatologia da endometriose. Métodos Um estudo caso-controle foi realizado com 40 mulheres diagnosticadas com endometriose e 15 mulheres férteis e saudáveis. Amostras pareadas de endométrio eutópico e de lesões endometrióticas (implantes endometrióticos peritoneais e ovarianos) foram obtidas de mulheres com endometriose nas fases proliferativa (n = 20) ou secretora (n = 20) do ciclo menstrual. Como controle, amostras pareadas de biópsia endometrial foram coletadas de mulheres saudáveis nas fases proliferativa (n = 15) e secretora (n = 15) nomesmo ciclomenstrual. Foram analisados os níveis de expressão dos genes CD63, S100A6 e GNB2L1 por reação em cadeia da polimerase em tempo real. Resultados Foi observado um aumento nos níveis de transcritos dos genes CD63, S100A6 e GNB2L1 em implantes ectópicos quando comparado ao endométrio eutópico de mulheres com e sem endometriose, independente da fase do ciclo menstrual. Conclusão Estes achados sugerem que os genes CD63, S100A6 e GNB2L1 podem estar envolvidos na patogênese da endometriose, pois participam de mecanismos como inibição de apoptose, angiogênese e proliferação celular, os quais levam à perda da homeostase celular no endométrio ectópico e, portanto, contribuem para o implante e a sobrevivência do tecido no ambiente extrauterino.

Humans , Female , Adult , Apoptosis/genetics , Cell Cycle Proteins/genetics , Cell Proliferation/genetics , Endometriosis/genetics , Endometriosis/pathology , Tetraspanin 30/genetics , S100 Calcium Binding Protein A6/genetics , Receptors for Activated C Kinase/genetics , Neoplasm Proteins/genetics , Neovascularization, Pathologic/genetics , Case-Control Studies , Gene Expression
Clinics ; 73(supl.1): e476s, 2018. graf
Article in English | LILACS | ID: biblio-952839


Gene therapy has been evaluated for the treatment of prostate cancer and includes the application of adenoviral vectors encoding a suicide gene or oncolytic adenoviruses that may be armed with a functional transgene. In parallel, versions of adenoviral vector expressing the p53 gene (Ad-p53) have been tested as treatments for head and neck squamous cell carcinoma and non-small cell lung cancer. Although Ad-p53 gene therapy has yielded some interesting results when applied to prostate cancer, it has not been widely explored, perhaps due to current limitations of the approach. To achieve better functionality, improvements in the gene transfer system and the therapeutic regimen may be required. We have developed adenoviral vectors whose transgene expression is controlled by a p53-responsive promoter, which creates a positive feedback mechanism when used to drive the expression of p53. Together with improvements that permit efficient transduction, this new approach was more effective than the use of traditional versions of Ad-p53 in killing prostate cancer cell lines and inhibiting tumor progression. Even so, gene therapy is not expected to replace traditional chemotherapy but should complement the standard of care. In fact, chemotherapy has been shown to assist in viral transduction and transgene expression. The cooperation between gene therapy and chemotherapy is expected to effectively kill tumor cells while permitting the use of reduced chemotherapy drug concentrations and, thus, lowering side effects. Therefore, the combination of gene therapy and chemotherapy may prove essential for the success of both approaches.

Humans , Male , Prostatic Neoplasms/therapy , Genetic Therapy/methods , Adenoviridae/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Genetic Vectors/therapeutic use , Lung Neoplasms/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/immunology , Tumor Suppressor Protein p53/biosynthesis , Prostate-Specific Antigen/genetics , Genes, Transgenic, Suicide , Neoplasm Proteins/genetics
Braz. j. med. biol. res ; 50(1): e5933, 2017. graf
Article in English | LILACS | ID: biblio-839243


Iodine-131 (131I) is widely used for the treatment of thyroid-related diseases. This study aimed to investigate the expression of p53 and BTG2 genes following 131I therapy in thyroid cancer cell line SW579 and the possible underlying mechanism. SW579 human thyroid squamous carcinoma cells were cultured and treated with 131I. They were then assessed for 131I uptake, cell viability, apoptosis, cell cycle arrest, p53 expression, and BTG2 gene expression. SW579 cells were transfected with BTG2 siRNA, p53 siRNA and siNC and were then examined for the same aforementioned parameters. When treated with a JNK inhibitor of SP600125 and 131I or with a NF-κB inhibitor of BMS-345541 and 131I, non-transfected SW579 cells were assessed in JNK/NFκB pathways. It was observed that 131I significantly inhibited cell proliferation, promoted cell apoptosis and cell cycle arrest. Both BTG2 and p53 expression were enhanced in a dose-dependent manner. An increase in cell viability by up-regulation in Bcl2 gene, a decrease in apoptosis by enhanced CDK2 gene expression and a decrease in cell cycle arrest at G0/G1 phase were also observed in SW579 cell lines transfected with silenced BTG2 gene. When treated with SP600125 and 131I, the non-transfected SW579 cell lines significantly inhibited JNK pathway, NF-κB pathway and the expression of BTG2. However, when treated with BMS-345541 and 131I, only the NF-κB pathway was suppressed. 131I suppressed cell proliferation, induced cell apoptosis, and promoted cell cycle arrest of thyroid cancer cells by up-regulating B-cell translocation gene 2-mediated activation of JNK/NF-κB pathways.

Humans , Apoptosis/drug effects , Cell Proliferation/drug effects , Iodine Radioisotopes/therapeutic use , MAP Kinase Signaling System , Neoplasm Proteins/genetics , Thyroid Neoplasms/drug therapy , Cell Line, Tumor , Iodine Radioisotopes/pharmacology , Neoplasm Proteins/metabolism , Polymerase Chain Reaction , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology
Biol. Res ; 50: 40, 2017. graf
Article in English | LILACS | ID: biblio-950887


BACKGROUND: Programmed cell death 5 (PDCD5) is an apoptosis-related gene cloned from TF-1 cells whose primary biological functions are to promote apoptosis and immune regulation. The effects and mechanisms exerted by key mediators of arthritic inflammation remain unclear in PDCD5 transgenic (PDCD5 tg) mice. RESULTS: In the current study, PDCD5 tg mice inhibited the progression of adjuvant-induced arthritis, specifically decreasing clinical signs and histological damage, compared with arthritis control mice. Additionally, the ratio of CD4+IFN-γ+ cells (Th1) and CD4+IL-17A+ cells (Th17), as well as the mRNA expression of the pro-inflammatory mediators IFN-γ, IL-6, IL-17A and TNF-α, were decreased in PDCD5 tg mice, while CD4+CD25+Foxp3+ regulatory T (Treg) cells and the anti-inflammatory mediators IL-4 and IL-10 were increased. Furthermore, PDCD5 tg mice demonstrated reduced serum levels of IFN-γ, IL-6, IL-17A and TNF-α and increased levels of IL-4. CONCLUSIONS: Based on our data, PDCD5 exerts anti-inflammatory effects by modifying the T lymphocytes balance, inhibiting the production of pro-inflammatory mediators and promoting the secretion of anti-inflammatory cytokines, validating PDCD5 protein as a possible treatment for RA.

Animals , Male , Mice , Arthritis, Experimental/metabolism , T-Lymphocytes, Regulatory/physiology , Apoptosis Regulatory Proteins/physiology , Neoplasm Proteins/physiology , Arthritis, Experimental/immunology , Mice, Transgenic , Apoptosis Regulatory Proteins/genetics , Mice, Inbred C57BL , Neoplasm Proteins/genetics
Biomédica (Bogotá) ; 36(4): 593-602, dic. 2016. tab, graf
Article in Spanish | LILACS | ID: biblio-950925


RESUMEN Introducción. La cadherina E (CDH1) cumple un papel importante en la transición epitelio-mesénquima y está relacionada con la invasión y las metástasis en varios tipos de carcinomas. Sin embargo, el efecto de las mutaciones y 'epimutaciones' germinales en la propensión al cáncer de mama no es claro. Objetivo. Evaluar el polimorfismo rs5030625, los cambios en el patrón de metilación del promotor y la expresión en la transcripción del gen CDH1 en pacientes con cáncer de mama. Materiales y métodos. Se tomaron muestras de sangre periférica de 102 pacientes con cáncer de mama y 102 mujeres de control. La genotipificación del polimorfismo rs5030625 se hizo mediante reacción en cadena de la polimerasa (PCR) y análisis de polimorfismos de longitud del fragmento de restricción; la PCR y el análisis de disociación de alta resolución sensible a metilación se emplearon para determinar el estado y el nivel de metilación del promotor del CDH1; por último, el nivel de expresión en la transcripción del CDH1 se evaluó mediante PCR cuantitativa con transcripción inversa. Resultados. Los resultados no evidenciaron asociación entre el polimorfismo rs5030625 y el cáncer de mama. Se encontraron perfiles aberrantes de metilación del promotor del CDH1 en las pacientes con cáncer de mama relacionados con las primeras etapas de desarrollo del cáncer. La disminución de la expresión del CDH1 se asoció con la presencia de metástasis y el estado de metilación del promotor. Conclusión. Las alteraciones en el CDH1 se asociaron con la invasión y las metástasis en el cáncer de mama. Se proporcionó evidencia adicional sobre la relevancia del CDH1 en el desarrollo y la progresión del cáncer de mama.

ABSTRACT Introduction: Cadherin-E (CDH1) is an important regulator of epithelial-mesenchymal transition, invasion and metastasis in many carcinomas. However, germinal epimutations and mutations effect in breast cancer susceptibility is not clear. Objective: To evaluate rs334558 polymorphism, promoter methylation status and CDH1 expression profile in breast cancer patients. Materials and methods: We collected peripheral blood samples from 102 breast cancer patients and 102 healthy subjects. The identification of rs334558 polymorphism was performed using PCR-RFLP, while methylation-specific PCR (MSP) and methylation-sensitive high-resolution melting (MS-HRM) were used to explore CDH1 methylation status; finally, CDH1 transcriptional expression profile was evaluated using RT-qPCR. Results: We found no association between rs334558 polymorphism and breast cancer. Aberrant promoter methylation profile was found in breast cancer patients and it was related with early cancer stages. CDH1 down-regulation was significantly associated with metastasis and promoter methylation. Conclusion: CDH1 alterations were associated with invasion and metastasis in breast cancer. Our results offer further evidence of CDH1 relevance in breast cancer development and progression.

Aged , Female , Humans , Middle Aged , Transcription, Genetic , Breast Neoplasms/genetics , Cadherins/genetics , Gene Expression Regulation, Neoplastic , Polymorphism, Single Nucleotide , Neoplasm Proteins/genetics , Breast Neoplasms/epidemiology , DNA, Neoplasm/genetics , DNA, Neoplasm/chemistry , RNA, Messenger/biosynthesis , RNA, Neoplasm/genetics , Antigens, CD , Cadherins/biosynthesis , Cadherins/physiology , Risk Factors , Promoter Regions, Genetic , Reproductive History , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/epidemiology , DNA Methylation , Genetic Predisposition to Disease , Epigenesis, Genetic , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/physiology
Article in English | WPRIM | ID: wpr-34234


Store-operated calcium (Ca2+) entry (SOCE) is the principal Ca2+ entry route in non-excitable cells, including cancer cells. We previously demonstrated that Orai1 and STIM1, the molecular components of SOCE, are involved in tumorigenesis of clear cell renal cell carcinoma (CCRCC). However, a clinical relevance of Orai1 and STIM1 expression in CCRCC has been ill-defined. Here, we investigated the expression of Orai1 and STIM1 in CCRCC, and compared their expression with clinico-pathological parameters of CCRCC and the patients' outcome. Immunohistochemical staining for Orai1 and STIM1 was performed on 126 formalin fixed paraffin embedded tissue of CCRCC and western blot analysis for Orai1 was performed on the available fresh tissue. The results were compared with generally well-established clinicopathologic prognostic factors in CCRCC and patient survival. Membrane protein Orai1 is expressed in the nuclei in CCRCC, whereas STIM1 shows the cytosolic expression pattern in immunohistochemical staining. Orai1 expression level is inversely correlated with CCRCC tumor grade, whereas STIM1 expression level is not associated with tumor grade. The higher Orai1 expression is significantly associated with lower Fuhrman nuclear grade, pathologic T stage, and TNM stage and with favorable prognosis. The expression level of STIM1 is not correlated with CCRCC grade and clinical outcomes. Orai1 expression in CCRCC is associated with tumor progression and with favorable prognostic factors. These results suggest that Orai1 is an attractive prognostic marker and therapeutic target for CCRCC.

Adolescent , Adult , Aged , Blotting, Western , Carcinoma, Renal Cell/diagnosis , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Kidney Neoplasms/metabolism , Male , Middle Aged , Neoplasm Proteins/genetics , ORAI1 Protein/genetics , Prognosis , Retrospective Studies , Stromal Interaction Molecule 1/genetics , Young Adult
ABCD arq. bras. cir. dig ; 28(1): 74-80, 2015. tab, graf
Article in English | LILACS | ID: lil-742762


INTRODUCTION: Gastric bypass is today the most frequently performed bariatric procedure,but, despite of it, several complications can occur with varied morbimortality. Probably all bariatric surgeons know these complications, but, as bariatric surgery continues to spread, general surgeon must be familiarized to it and its management. Gastric bypass complications can be divided into two groups: early and late complications, taking into account the two weeks period after the surgery. This paper will focus the early ones. METHOD: Literature review was carried out using Medline/PubMed, Cochrane Library, SciELO, and additional information on institutional sites of interest crossing the headings: gastric bypass AND complications; follow-up studies AND complications; postoperative complications AND anastomosis, Roux-en-Y; obesity AND postoperative complications. Search language was English. RESULTS: There were selected 26 studies that matched the headings. Early complications included: anastomotic or staple line leaks, gastrointestinal bleeding, intestinal obstruction and incorrect Roux limb reconstruction. CONCLUSION: Knowledge on strategies on how to reduce the risk and incidence of complications must be acquired, and every surgeon must be familiar with these complications in order to achieve an earlier recognition and perform the best intervention. .

INTRODUÇÃO: O bypass gástrico é hoje o procedimento bariátrico mais realizado, mas, apesar disso, várias complicações podem ocorrer com variada morbimortalidade. Provavelmente todos os cirurgiões bariátricos conhecem essas complicações, mas como a cirurgia bariátrica continua a se espalhar, o cirurgião geral deve estar familiarizado com essas complicações e seu manuseio. As complicações do bypass gástrico podem ser divididas em dois grupos: as precoces e tardias, tendo em conta o período de duas semanas após a operação. Este artigo irá focar as precoces. MÉTODO: Foi realizada revisão da literatura utilizando as bases Medline/PubMed, Cochrane Library, SciELO, e informações adicionais sobre sites institucionais de interesse cruzando os descritores: bypass gástrico AND complicações; seguimento AND complicações; complicações pós-operatórias AND anastomose, Roux-en-Y; obesidade AND complicações pós-operatórias. A língua usada para a busca foi o inglês. RESULTADOS: Foram selecionados 26 artigos que combinavam com os descritores. As complicações imediatas foram: fístula na linha de grampeamento, sangramento gastrointestinal, obstrução intestinal e reconstrução incorreta da alça em Roux. CONCLUSÃO: O conhecimento sobre as estratégias de como reduzir o risco e incidência das complicações deve ser adquirido ao longo do tempo, e cada cirurgião deve estar familiarizado com essas complicações, a fim de reconhecê-las precocemente e realizar a melhor intervenção. .

Animals , Female , Mice , B-Lymphocytes/physiology , Poly(ADP-ribose) Polymerases/physiology , Antibody Formation/drug effects , Antibody Formation/genetics , Apoptosis/genetics , Apoptosis/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/metabolism , Cell Differentiation/drug effects , Cell Differentiation/genetics , Cell Survival/genetics , Immunoglobulin A/immunology , /pharmacology , Mice, Knockout , Multigene Family , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Neoplasm Proteins/physiology , Poly(ADP-ribose) Polymerases/chemistry , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Sequence Homology
Biol. Res ; 48: 1-7, 2015. ilus, graf
Article in English | LILACS | ID: biblio-950782


BACKGROUND: Ubiquitin Specific Peptidase 39 (USP39) is a 65 kDa SR-related protein involved in RNA splicing. Previous studies showed that USP39 is related with tumorigenesis of human breast cancer cells. RESULTS: In the present study, we investigated the functions of USP39 in human hepatocellular carcinoma (HCC) cell line SMMC-7721. We knocked down the expression of USP39 through lentivirus mediated RNA interference. The results of qRT-PCR and western blotting assay showed that both the mRNA and protein levels were suppressed efficiently after USP39 specific shRNA was delivered into SMMC-7721 cells. Cell growth was significantly inhibited as determined by MTT assay. Crystal violet staining indicated that colony numbers and sizes were both reduced after knock-down of USP39. Furthermore, suppression of USP39 arrested cell cycle progression at G2/M phase in SMMC-7721cells. In addition, Annexin V showed that downregulation of USP39 significantly increased the population of apoptotic cells. CONCLUSIONS: All our results suggest that USP39 is important for HCC cell proliferation and is a potential target for molecular therapy of HCC.

Humans , Cell Cycle , Carcinoma, Hepatocellular/pathology , Lentivirus/genetics , RNA Interference/physiology , Cell Proliferation , Ubiquitin-Specific Proteases/metabolism , Liver Neoplasms/pathology , Neoplasm Proteins/metabolism , In Vitro Techniques , Gene Expression Regulation, Neoplastic/genetics , Cell Cycle/genetics , Blotting, Western , Apoptosis , Gene Transfer Techniques , Carcinoma, Hepatocellular/enzymology , Gene Silencing , Cell Line, Tumor , Cell Proliferation/genetics , Gene Knockdown Techniques , Real-Time Polymerase Chain Reaction , Ubiquitin-Specific Proteases/genetics , Liver Neoplasms/enzymology , Neoplasm Proteins/genetics
Article in English | WPRIM | ID: wpr-195226


BACKGROUND/AIMS: Gout is a common inf lammatory arthritis triggered by the crystallization of uric acid in the joints. Serum uric acid levels are highly heritable, suggesting a strong genetic component. Independent studies to confirm the genetic associations with gout in various ethnic populations are warranted. We investigated the association of polymorphisms in the ABCG2 and SLC2A9 genes with gout in Korean patients and healthy individuals. METHODS: We consecutively enrolled 109 patients with gout and 102 healthy controls. The diagnosis of gout was based on the preliminary criteria of the America College of Rheumatology. Genomic DNA was extracted from whole blood samples. We identified single nucleotide polymorphism (SNP) changes in the ABCG2 and SLC2A9 genes using a direct sequencing technique. rs2231142 in ABCG2 and rs6449213 and rs16890979 in SLC2A9 and nearby regions were amplified by polymerase chain reaction. RESULTS: Patients with gout had significantly higher A/A genotype (29.3% vs. 4.9%, respectively) and A allele (52.8% vs. 26.5%, respectively) frequencies of rs2231142 in ABCG2 than did controls (chi2 = 29.42, p G and c.1002+78G>A) in the SLC2A9 gene. The univariate logistic regression analysis revealed that the c.881A>G and c.1002+78G>A SNPs were significantly higher in patients than in controls. CONCLUSIONS: We demonstrated a significant association between rs2231142 in the ABCG2 gene and gout and identified novel SNPs, c.881A>G and c.1002+78G>A, in the SLC2A9 gene that may be associated with gout in a Korean population.

ATP-Binding Cassette Transporters/genetics , Arthritis, Gouty/blood , Asians/genetics , Biomarkers/blood , Case-Control Studies , Chi-Square Distribution , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Glucose Transport Proteins, Facilitative/genetics , Haplotypes , Humans , Logistic Models , Neoplasm Proteins/genetics , Odds Ratio , Phenotype , Polymorphism, Single Nucleotide , Republic of Korea , Risk Factors , Uric Acid/blood
Article in Korean | WPRIM | ID: wpr-186433


The aim of this study was to analyze the use of 12 single-nucleotide polymorphisms in genes ELAC2, RNASEL and MSR1 as biomarkers for prostate cancer (PCa) detection and progression, as well as perform a genetic classification of high-risk patients. A cohort of 451 men (235 patients and 216 controls) was studied. We calculated means of regression analysis using clinical values (stage, prostate-specific antigen, Gleason score and progression) in patients and controls at the basal stage and after a follow-up of 72 months. Significantly different allele frequencies between patients and controls were observed for rs1904577 and rs918 (MSR1 gene) and for rs17552022 and rs5030739 (ELAC2). We found evidence of increased risk for PCa in rs486907 and rs2127565 in variants AA and CC, respectively. In addition, rs627928 (TT-GT), rs486907 (AG) and rs3747531 (CG-CC) were associated with low tumor aggressiveness. Some had a weak linkage, such as rs1904577 and rs2127565, rs4792311 and rs17552022, and rs1904577 and rs918. Our study provides the proof-of-principle that some of the genetic variants (such as rs486907, rs627928 and rs2127565) in genes RNASEL, MSR1 and ELAC2 can be used as predictors of aggressiveness and progression of PCa. In the future, clinical use of these biomarkers, in combination with current ones, could potentially reduce the rate of unnecessary biopsies and specific treatments.

Aged , Aged, 80 and over , Cohort Studies , Disease Progression , Endoribonucleases/genetics , Gene Frequency , Genetic Markers/genetics , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Neoplasm Proteins/genetics , Polymorphism, Single Nucleotide , Prognosis , Prostate/metabolism , Prostatic Neoplasms/diagnosis , Scavenger Receptors, Class A/genetics
Salud colect ; 10(3): 353-363, sep.-dic. 2014.
Article in Spanish | LILACS | ID: lil-733295


El objetivo de este artículo es analizar las relaciones entre profesionales de la salud y usuarios/as desde la perspectiva de género. A partir del referencial teórico de Pierre Bourdieu, se retoman y analizan críticamente datos de dos investigaciones realizadas en Brasil de la cuales participamos como autores: la primera, realizada en la ciudad de Río de Janeiro y, la segunda, un estudio multicéntrico y de naturaleza etnográfica desarrollado en ocho servicios distribuidos en cuatro estados brasileños, dos de la región Sudeste y dos de la Nordeste. Entre los principales resultados se destaca que las relaciones entre profesionales de la salud y usuarios/as, aunque estén marcadas por opiniones divergentes, están atravesadas por un habitus "generificado". Se concluye, entre otros aspectos, que la construcción de las diversas feminidades y masculinidades y la forma en que se da el ejercicio de estas en los contextos asistenciales de la salud son producto de un proceso que es, al mismo tiempo, socio-histórico y personal.

The objective of this article is to analyze relationships between health professionals and users from a gender perspective. Using Pierre Bourdieu as a theoretical reference, we critically analyze data from two studies carried out in Brazil in which we took part as authors. The first of these studies was based in Rio de Janeiro and the second was a multicenter and ethnographical study carried out in eight health care facilities distributed throughout four Brazilian states, two in the Southeast region and two in the Northeast region. Among the principal results of the present study, we found that although the relationships between health professionals and users demonstrate varied opinions, all are marked by a gendered habitus. We conclude that, among other aspects, the construction of diverse femininities and masculinities and the way in which these are exercised in health care contexts are the product of process that is both socio-historical and personal.

Humans , Esophageal Neoplasms/chemistry , Neoplasm Proteins/analysis , Cell Line, Transformed , Electrophoresis, Gel, Two-Dimensional , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/genetics , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Article in English | IMSEAR | ID: sea-157088


Background & objectives: Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumour suppressor genes. O6-methyguanine-DNA methyltransferase (MGMT) is a DNA repair gene that removes mutagenic and cytotoxic adducts from the O6-position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression has been found in some primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT gene and its relation with MGMT protein expression in human epithelial ovarian carcinoma. Methods: A total of 88 epithelial ovarian cancer (EOC) tissue samples, 14 low malignant potential (LMP) tumours and 20 benign ovarian tissue samples were analysed for MGMT promoter methylation by nested methylation-specific polymerase chain reaction (MSP) after bisulphite modification of DNA. A subset of 64 EOC samples, 10 LMP and benign tumours and five normal ovarian tissue samples were analysed for protein expression by immunohistochemistry. Results: The methylation frequencies of the MGMT gene promoter were found to be 29.5, 28.6 and 20 per cent for EOC samples, LMP tumours and benign cases, respectively. Positive protein expression was observed in 93.8 per cent of EOC and 100 per cent in LMP, benign tumours and normal ovarian tissue samples. Promoter hypermethylation with loss of protein expression was seen only in one case of EOC. Interpretation & conclusions: Our results suggest that MGMT promoter hypermethylation does not always reflect gene expression.

Adult , Aged , DNA Methylation/genetics , DNA Modification Methylases/biosynthesis , DNA Modification Methylases/genetics , DNA Repair Enzymes/biosynthesis , DNA Repair Enzymes/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Middle Aged , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Ovarian Neoplasms/genetics , Promoter Regions, Genetic , Tumor Suppressor Proteins/biosynthesis , Tumor Suppressor Proteins/genetics
São Paulo; s.n; 2014. [167] p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: lil-790389


INTRODUÇÃO: O carcinoma adrenocortical é uma neoplasia rara que carreia um prognóstico reservado. Recentemente, uma série de estudos demonstrou o potencial do perfil de miRNAs na diferenciação entre adenomas e carcinomas adrenocorticais, estratificação de risco e prognóstico. Entretanto, pouco se sabe ainda sobre a regulação pós-transcricional de miRNAs. Nesse contexto, o LIN28 é uma proteína ligadora de RNAs altamente conservada que surgiu como um modulador do let-7, uma importante família de miRNAs amplamente conhecida por seus efeitos supressivos tumorais. Além do let-7, o LIN28 também mostrou regular e ser regulado pelo mir-9, mir-30 e mir-125. OBJETIVOS: Analisar a expressão gênica e proteica do LIN28 em uma grande coorte de tumores adrenocorticais (TACs) de adultos e pediátricos, além de investigar a variação no número de cópias dos genes LIN28A e LIN28B e a expressão dos miRNAs regulatórios do LIN28 (família let-7, mir-9, mir-30 e mir-125) em um subgrupo desta coorte. MÉTODOS: A expressão proteica do LIN28 foi avaliada em um total de 266 TACs de adultos (78 adenomas e 188 carcinomas) e 44 pediátricos (35 clinicamente benignos e 9 clinicamente malignos). A expressão dos genes LIN28A e LIN28B foi avaliada em um subgrupo de 86 TACs adultos e pediátricos e a análise da variação no número de cópias destes genes em 58 TACs. O estudo de expressão das famílias dos miRNAs let-7, mir-9, mir-30 e mir-125 foi realizado em 28 carcinomas adrenocorticais de adultos. RESULTADOS: Em adultos, o gene LIN28A mostrou-se hiperexpresso em carcinomas agressivos quando comparado a adenomas [7,0 (0 a 174,3) vs. 3,6 (0 a 18,3); p = 0,006, respectivamente] e observou-se uma tendência a maior expressão quando comparados a carcinomas não agressivos [7,0 (0 a 174,3) vs. 7,1 (0 a 17,1); p = 0,092]. A expressão do LIN28B foi negativa na grande maioria (92%) dos TACs de adultos. Curiosamente, uma imunorreatividade fraca para o LIN28 foi significativamente associada com...

INTRODUCTION: Adrenocortical carcinoma is a rare neoplasm with overall poor prognosis. Recently, several studies demonstrated the potential of miRNA profiling in differentiating between adrenocortical adenomas and carcinomas, risk stratification and prognosis. Nevertheless, little is known about posttranscriptional regulation of miRNAs. LIN28 is a highly conserved RNA-binding protein that has emerged as a modulator of the processing of let-7, an important family of miRNAs widely known for its tumor-suppressive effects. Besides from let-7, LIN28 has also shown to regulate and be regulated by mir-9, mir-30 and mir-125. OBJECTIVES: To analyze LIN28 gene and protein expression in a large cohort of adult and pediatric adrenocotical tumors (ACTs), and investigate the copy number variation analysis for LIN28A and LIN28B genes and the expression of LIN28 regulatory microRNAs (let-7 family, mir-9, mir-30 e mir-125) in a subgroup of this cohort. METHODS: LIN28 protein expression was assessed in a total of 266 adult (78 adenomas and 188 carcinomas) and 44 pediatric ACTs (35 clinically benign and 9 clinically malignant). LIN28A and LIN28B gene expression was evaluated in a subgroup of 86 adult and pediatric ACTs and copy number variation analysis of these genes in 58 ACTs. The expression of let-7 family, mir-9, mir-30 and mir-125 was performed in 28 adult carcinomas. RESULTS: In adults, LIN28A gene was overexpressed in aggressive carcinomas when compared with adenomas [7.0 fold change (from 0 to 174.3) vs. 3.6 (from 0 to 18.3); p = 0.006, respectively] and a trend towards greaten expression when compared with non-aggressive carcinomas [7.0 (from 0 to 174.3) vs. 7.1 (from 0 to 17.1); p = 0.092]. LIN28B expression was undetectable in the great majority (92%) of adult ACTs. Surprisingly, weak LIN28 staining was significantly associated with reduced disease-free survival in this population (p = 0.01), but for overall survival only a trend was detectable (p= 0.117). In...

Humans , Male , Female , Child , Adult , Biomarkers, Tumor/genetics , Carcinogenesis/genetics , Adrenocortical Carcinoma/genetics , Gene Expression , MicroRNAs/genetics , Prognosis , RNA-Binding Proteins/metabolism , Neoplasm Proteins/genetics , Gene Expression Regulation, Neoplastic/genetics , Survival
Biol. Res ; 47: 1-11, 2014. tab
Article in English | LILACS | ID: biblio-950736


BACKGROUND: Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set. RESULTS: Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10mm) to house dust (1.4-fold) and storage mite (7.8-fold). CONCLUSION: In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.

Humans , Male , Female , Child , Adolescent , Polymorphism, Genetic/genetics , Asthma/genetics , Portugal , Severity of Illness Index , Biomarkers , Case-Control Studies , Vital Capacity/genetics , Forced Expiratory Volume/genetics , Risk Factors , Interleukin-4/analysis , Interleukin-4/genetics , Receptors, Adrenergic, beta-2/analysis , Receptors, Adrenergic, beta-2/genetics , Statistics, Nonparametric , Interleukin-13/analysis , Interleukin-13/genetics , Disintegrins/analysis , Disintegrins/genetics , Polymorphism, Single Nucleotide/genetics , ADAM Proteins/analysis , ADAM Proteins/genetics , STAT6 Transcription Factor/analysis , STAT6 Transcription Factor/genetics , Genotype , Neoplasm Proteins/analysis , Neoplasm Proteins/genetics