RESUMO
BACKGROUND@#Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis.@*METHODS@#We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results.@*RESULTS@#We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935-0.987, P = 3.57E-03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936-0.995, P = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941-0.983, P = 5.11E-04; ENEC, OR = 0.964, 95% CI = 0.940-0.989, P = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918-0.986, P = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859-0.976, P = 0.002). The statistical powers of positive MR results were all >0.9.@*CONCLUSION@#This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.
Assuntos
Feminino , Humanos , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neoplasias Hormônio-Dependentes , Reprodutibilidade dos Testes , Neoplasias do Endométrio , Lúpus Eritematoso Sistêmico/genética , Carcinoma Endometrioide , Neoplasias da Mama , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Hormone-dependent breast cancer has growth factors that respond positively to the hormones estrogen and progesterone. Thus, adjuvant endocrine therapy causes decreased or undetectable serum levels of these hormones. However, this treatment can have side effects that compromise the sexual health of patients, such as dyspareunia, vaginal dryness and decreased libido. In this scenario, the objective of this work was to document the main outcomes in sexuality in women after treatment for hormonepositive breast cancer. Thus, this is an integrative literature review, in which the following databases were used: U.S. National Library of Medicine (PubMed), Virtual Health Library (BVS), SCOPUS and Scientific Electronic Library Online (SCIELO), using the descriptors: "sexuality", "antineoplastic agents, hormonal" and "breast neoplasms", joined by the Boolean operator "AND". Full articles published in the last 5 years (2017-2022) were included; written in Portuguese or English. Articles dealing with non-hormone-dependent or metastatic breast cancer, or with patients younger than 18 years, or articles that did not answer the research question were excluded. In total, 26 articles were identified, of which 7 comprised the final sample of this review. A total of 3,850 women participated in the included studies. The main sexual dysfunctions found were: dyspareunia, hot flashes, decreased libido, vaginal dryness, breast tenderness, self-image concerns and hair loss. The symptom vaginal dryness was the most prevalent, mentioned in 71.4% of the articles included. In view of the adverse effects listed in this review, there is a need to carry out more studies on this topic, since the diagnosis of this comorbidity brings clinical, psychological, emotional, sociocultural and economic outcomes for the patient. Thus, a multidisciplinary team must assertively address these complaints to improve the overall quality of life of these women (AU)
Assuntos
Humanos , Feminino , Disfunções Sexuais Fisiológicas/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos Hormonais/uso terapêutico , Sexualidade/efeitos dos fármacos , Neoplasias Hormônio-Dependentes/tratamento farmacológicoRESUMO
Introducción y Objetivos El cáncer de próstata es la segunda causa de mortalidad por cáncer en hombres en Colombia y en el mundo. El efecto "vanishing" en cáncer de próstata, es un fenómeno poco frecuente que se define como la ausencia de tumor en el estudio histológico postquirúrgico de pacientes llevados a prostatectomía radical como manejo curativo diagnóstico previo confirmado por biopsia o RTUP. Su incidencia en diferentes series llega hasta el 0,86%, por lo cual existen pocos estudios aleatorizados al respecto y aún no es clara la conducta con ese tipo de tumores. Reportamos un caso de un paciente con cáncer de próstata pT0 y realizamos una revisión de la literatura respecto del seguimiento y manejo que se deberían seguir al enfrentarnos a ese tipo de tumor. Métodos y Materiales Revisión de la literatura y reporte de caso clínico. Reporte de Caso Hombre de 58 años sintomático urinario, con PSA elevado por lo que se realizó biopsia transrectal de próstata, con resultado de adenocarcinoma de próstata confirmado por inmunohistoquímica. Al realizarse la prostatectomía radical no se encuentra tumor en la patología. En la literatura se encuentran factores asociados con la presencia del tumor cuando hay RTUP previa y uso de hormonoterapia neoadyuvante en el contexto de tumores de bajo volumen. A pesar de no encontrarse tumor en la patología, está descrita la recaída bioquímica y progresión clínica de esos tumores, por lo que debe realizarse el seguimiento usual para esa patología. Conclusiones El hallazgo de pT0 en cáncer de próstata, aunque poco frecuente, demanda una guía de manejo Proponemos la revisión de la patología con el protocolo descrito para reducir los falsos positivos y el seguimiento usual con los pasos estandarizados en las guías internacionales.
Introduction and Objectives Prostate cancer is the second leading cause of death related with cancer in men in Colombia and the world. "Vanishing" phenomenon in prostate cáncer is a rare event, where the post-surgical histologic review in patiets that underwent radical prostatectomy is negative, all of them with previous diagnosis of CaP by biopsy or TUR. The incidence of CaP in different series reaches 0.86%, whereby there are few randomized studies and the management and follow up of this type of tumors is not clear. In this article we report a case of a pT0 prostate cancer patient. We perform a systematic review of the literature to determine the medical behavior and medical follow up in cases presenting with pT0 prostate cancer. Materials and Methods Review of the literature & case report. Results Patient of 58 years old with medical history of recent progressive LUTS and high PSA levels that underwent a trans-rectal prostate biopsy with report of adenocarcinoma, that were confirmed by immunohistochemistry. In the pathology report after the radical prostatectomy no tumor cells were found. In the literature, there is reference about factors associated with pT0 prostate cancer in patients with previous RTUP and that were taken to hormonal coadjutant therapy in lesser degree tumors. Despite the absent of cancer findings in the pathology, it is well described biochemistry relapses and clinical progression of this tumors; usual protocol follow up must be made. Conclusion In patients with pT0 prostate cancer, even though to be a rare finding, must be studied and follow up with the steps mentioned above with the aim to reduce the false positive cases. Also the follow-ups steps must fully meet the requirements of standardized protocols guidelines.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia , Neoplasias da Próstata , Guias como Assunto , Ressecção Transuretral da Próstata , Patologia , Biópsia , Imuno-Histoquímica , Adenocarcinoma , Causas de Morte , Neoplasias Hormônio-DependentesRESUMO
Glycogen synthase kinase3 (GSK3α and GSK3β) are serine/threonine protein kinases acting on numerous substrates and involved in the regulation of various cellular functions such as their proliferation, survival, glycogen metabolism, and autophagy. Accumulating evidence indicates that the expression of GSK3α is increased mainly in androgendependent while that of GSK3β in androgenindependent prostate cancer, and that GSK3β is also involved in the regulation of the transactivation of the androgen receptor (AR) and growth of prostate cancer. Animal experiments have proved that some GSK3 inhibitors, such as lithium, can significantly suppress tumor growth in different animal models of prostate cancer. The GSK3 inhibitor is promising to be an important agent for the clinical management of prostate cancer.
Assuntos
Animais , Humanos , Masculino , Androgênios , Linhagem Celular Tumoral , Quinase 3 da Glicogênio Sintase , Metabolismo , Glicogênio Sintase Quinase 3 beta , Metabolismo , Proteínas de Neoplasias , Metabolismo , Neoplasias Hormônio-Dependentes , Metabolismo , Neoplasias da Próstata , Tratamento Farmacológico , Patologia , Receptores Androgênicos , MetabolismoRESUMO
To evaluate the efficacy of adjuvant endocrine therapy (AET) in breast cancer patients with a positive-to-negative switch of hormone receptor status after neoadjuvant chemotherapy (NAC).One hundred and six patients who presented with hormone receptor (HR)-positive breast cancer at diagnosis and turned to HR-negative after NAC during December 2000 and December 2013 in Jiaxing Maternity and Child Health Care Hospital were retrospectively identified. Kaplan-Meier analysis and log-rank test were used for univariate analyses of factors related to disease free survival (DFS) and overall survival (OS). Multivariate analysis was carried out using the Cox proportional hazards model in patients with DFS and OS.All the patients were categorized into two groups on the basis of the administration of AET:61 AET-administered patients (57.5%) and 45 AET-naïve patients (42.5%). After a median follow-up of 68 months (range 14-103 months), human epidermal growth factor receptor 2 (HER-2) status, initial clinical stage, pathological axillary lymph node status and the use of AET were identified as the variables affecting DFS and OS (all<0.05). Patients treated with AET had a significantly improved 5-year DFS rate when compared with that without AET (77.1%53.5%,<0.05). The 5-year OS of AET-administered patients was also better than that of AET-naïve patients (80.9%71.0%,<0.05). Cox regression analysis showed that AET-administered or not was the independent predictor for 5-year DFS (=2.096, 95%:1.081-4.065,<0.05).Patients with HR altered from positive to negative after NAC may still gain benefit from AET.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Antineoplásicos Hormonais , Usos Terapêuticos , Axila , Neoplasias da Mama , Química , Classificação , Tratamento Farmacológico , Mortalidade , Quimioterapia Adjuvante , Métodos , Intervalo Livre de Doença , Estimativa de Kaplan-Meier , Linfonodos , Metástase Linfática , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Hormônio-Dependentes , Tratamento Farmacológico , Modelos de Riscos Proporcionais , Receptor ErbB-2 , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas , Tratamento FarmacológicoRESUMO
<p><b>Objective</b>To explore the expression of pituitary tumor transforming gene 1 (PTTG1) during the transformation of prostate cancer from androgen-dependent (ADPC) to androgen-independent (AIPC).</p><p><b>METHODS</b>We established an AIPC cell model LNCaP-AI by culturing the androgen-dependent LNCaP cell line in the hormone-deprived medium for over 3 months. The cell model was verified and the PTTG1 expression in the LNCaP cells was detected by Western blot and RT-PCR during hormone deprivation.</p><p><b>RESULTS</b>The AIPC cell model LNCaP-AI was successfully established. The PTTG1 expression was gradually increased in the LNCaP cells with the prolonged time of hormone deprivation and the expressions of matrix metalloproteinases MMP-2 and -9 were elevated at the same time.</p><p><b>CONCLUSIONS</b>The expression of PTTG1 is increased gradually in AIPC, which may be a target of gene therapy for advanced prostate cancer.</p>
Assuntos
Humanos , Masculino , Western Blotting , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Metaloproteinase 2 da Matriz , Metabolismo , Metaloproteinase 9 da Matriz , Metabolismo , Neoplasias Hormônio-Dependentes , Neoplasias da Próstata , Genética , Securina , GenéticaRESUMO
<p><b>OBJECTIVE</b>To investigate the expression of the Pim-1 gene in the LNCaP cells of the animal model of orthotopically implanted prostate cancer by surgical castration simulating androgen-deprivation therapy.</p><p><b>METHODS</b>We equally allocated 32 male BALBc-nu mice into 4 groups, androgen-dependent prostate cancer (ADPC), androgen-deprivation therapy (ADT) , castration-resistant prostate cancer (CRPC) and blank control, and established the models of orthotopically implanted tumor using human prostate cancer LNCaP cells. We detected and ,compared the expressions of Pim-1, PSA, and androgen receptor (AR) in the tumor tissues of different groups by RT-PCR. qRT-PCR, ELSIA and immunohistochemistry.</p><p><b>RESULTS</b>The relative gray scales in the ADPC and CRPC groups were 0.59 ± 0.01 and 1.14 ± 0.02, with statistically significant differences from 0.62 ± 0.03 in the ADT group (P < 0.05), and the Δ Ct values of Pim-1 were 6.15 ± 0.34 and 4.56 ± 0.23 in the former two groups, also with significant differences from 5.11 ± 0.21 in the latter (P < 0.05). The results of 2-ΔΔ Ct relative quantification analysis showed that the amplification products of Pim-1 in the ADT and CRPC groups increased 2.05 and 3.01 times respectively that of the ADPC group. The concentration of PSA was significantly higher in the ADPC ([480 ± 25] pg/ml) and CRPC ([870 ± 23] pg/ml) than in the ADT ([170 ± 32] pg/ml) and blank control groups (0 µg/L) (P < 0.01). The mean optical densities of Pim-1 and AR proteins were 0.017 ± 0.002 and 0.032 ± 0.009 in the ADPC group and 0.024 ± 0.002 and 0.040 ± 0.011 in the CRPC group, both with significant differences from those in the ADT group (0.018 ± 0.001 and 0.019 ± 0.006) (P < 0.01).</p><p><b>CONCLUSION</b>Pim-1 is highly expressed in nude mice with prostate cancer receiving androgen-deprivation therapy and plays an important role in the progression and metastasis of prostate cancer.</p>
Assuntos
Animais , Humanos , Masculino , Camundongos , Antagonistas de Androgênios , Usos Terapêuticos , Progressão da Doença , Expressão Gênica , Xenoenxertos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Hormônio-Dependentes , Metabolismo , Antígeno Prostático Específico , Metabolismo , Neoplasias de Próstata Resistentes à Castração , Genética , Metabolismo , Terapêutica , Proteínas Proto-Oncogênicas c-pim-1 , Metabolismo , Receptores Androgênicos , MetabolismoRESUMO
O artigo analisa o livro Boys in white: student culture in medical school, de Howard S. Becker, Blanche Geer, Everett C. Hughes e Anselm Strauss, considerado um dos modelos de pesquisa qualitativa em sociologia. A análise aborda as trajetórias dos autores, do livro, da pesquisa qualitativa e dos estudantes de medicina, enfatizando sua importância nas origens da sociologia médica e da sociologia da educação médica. Na trajetória dos autores são apresentados aspectos biobibliográficos; na da pesquisa qualitativa, o modo como essa metodologia de investigação atravessa a construção do trabalho de campo; e na dos estudantes, sua forma de atravessar os primeiros anos da escola médica e construir sua própria “cultura do estudante”.
This article analyzes Boys in white: student culture in medical schoolby Howard S. Becker, Blanche Geer, Everett C. Hughes and Anselm Strauss, considered a model of qualitative research in sociology. The analysis investigates the trajectories of the authors, the book, qualitative analysis, and the medical students, emphasizing their importance in the origins of medical sociology and the sociology of medical education. In the trajectory of the authors, bibliographical information is given. The trajectory of qualitative research focuses on how this methodology influences the construction of the field. The investigation of the students’ trajectory shows how they progress through their first years at medical school to build their own student culture.
Assuntos
Animais , Feminino , Camundongos , Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/farmacologia , Antineoplásicos Hormonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Estrogênios , Antagonistas de Estrogênios/farmacologia , Inibidores do Crescimento/farmacologia , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Fenilacetatos/farmacologia , /biossíntese , Tamoxifeno/farmacologia , Adenocarcinoma/patologia , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/patologia , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Sinergismo Farmacológico , Genes ras , Camundongos Nus , Transplante de Neoplasias , Neoplasias Hormônio-Dependentes/patologia , /fisiologia , Fenilacetatos/administração & dosagem , /genética , Transfecção , Tamoxifeno/administração & dosagem , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Wide spread use of Di-(2-ethylhexyl) phthalate (DEHP) has made it a ubiquitous contaminant in today’s environment, responsible for possible carcinogenic and endocrine disrupting effects. In the present investigation an integrative toxico-proteomic approach was made to study the estrogenic potential of DEHP. In vitro experiments carried out with DEHP (0.1-100 μM) induced proliferations (E-screen assay) in human estrogen receptors-α (ERα) positive MCF-7 and ERα negative MDA-MB-231 breast cancer cells irrespective of their ERα status. Further, DEHP suppressed tamoxifen (a potent anti-breast cancer drug) induced apoptosis in both cell types as shown by flowcytometric cell cycle analysis. Label-free quantitative proteomics analysis of the cell secretome of both the cell lines indicated a wide array of stress related, structural and receptor binding proteins that were affected due to DEHP exposure. The secretome of DEHP treated MCF-7 cells revealed the down regulation of lactotransferrin, an ERα responsive iron transport protein. The results indicated that toxicological effects of DEHP did not follow an ERα signaling pathway. However, the differential effects in MCF-7 and MDA-MB-231 cell lines indicate that ERα might have an indirect modulating effect on DEHP induced toxicity.
Assuntos
Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Dietilexilftalato/toxicidade , Poluentes Ambientais/toxicidade , Receptor alfa de Estrogênio/efeitos dos fármacos , Receptor alfa de Estrogênio/fisiologia , Estrogênios , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lactoferrina/biossíntese , Lactoferrina/genética , Lactoferrina/metabolismo , Células MCF-7/efeitos dos fármacos , Células MCF-7/metabolismo , Espectrometria de Massas/instrumentação , Microquímica/instrumentação , Proteínas de Neoplasias/efeitos dos fármacos , Proteínas de Neoplasias/fisiologia , Proteínas de Neoplasias/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Proteômica , Tamoxifeno/antagonistas & inibidores , Tamoxifeno/farmacologiaRESUMO
BACKGROUND/AIMS: The higher incidence of gallbladder cancer (GBC) in females has been accredited to the involvement of hormones. The clinical implications of sex hormone receptors in GBC are well established. Cysteine proteases (such as caspase-3-9, etc.) are known to play a central role in the apoptotic pathway. Of these, the downstream enzyme caspase-3 is often activated in the apoptotic pathway. The aim of this work was to examine the status of apoptosis (which directly correlated with the level of active caspase-3) in hormone-responsive GBC. METHODS: We used 10 androgen receptor (AR)-positive, 14 estrogen receptor (ER)-positive, 12 HER/neu-positive, eight triple positive, and 10 triple negative malignant GBC human tissue samples. We isolated the total cellular protein from tumor tissues and carried out Western blotting using antipro-caspase-3 and anti-activated caspase-3 antibodies. RESULTS: ER and HER/neu-positive GBC exhibited high caspase-3 activity and low procaspase-3 activity, whereas AR-positive GBC showed no significant level of apoptosis. We also evaluated the apoptosis status of triple positive GBC and triple negative GBC, and found significant apoptosis in triple positive GBC. CONCLUSIONS: The results indicate that ER and HER/neu-positive GBCs had active apoptosis, whereas AR-positive GBC was highly resistant to apoptosis.
Assuntos
Humanos , Antineoplásicos Hormonais/uso terapêutico , Apoptose/efeitos dos fármacos , Western Blotting , Carcinoma/tratamento farmacológico , Caspase 3/análise , Resistencia a Medicamentos Antineoplásicos , Ativação Enzimática , Neoplasias da Vesícula Biliar/tratamento farmacológico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Receptor ErbB-2/análise , Receptores Androgênicos/análise , Receptores de Estrogênio/análise , Biomarcadores Tumorais/análiseRESUMO
El cáncer de próstata presenta una progresión andrógeno-dependiente mediada por el receptor de andrógeno (AR), por lo que el bloqueo androgénico es la terapia estándar para su tratamiento en estado avanzado. Sin embargo, a pesar de una sensibilidad inicial, estos cánceres usualmente evolucionan hacia un estado hormono-resistente. Esta resistencia puede ser debida a una amplificación del gen AR, a sus mutaciones y al aumento en la expresión de proteínas co-activadoras. Igualmente, el receptor AR puede permanecer activo, independientemente de la fijación del ligando por fosforilación de factores de crecimiento y de citosinas. Adicionalmente, hay otras posibles vías independientes del receptor AR, como lo ejemplifica la adquisición del fenotipo neuroendocrino. En esta revisión se examinan tanto los mecanismos moleculares involucrados en la progresión del cáncer de próstata así como la forma en que sus células evaden la apoptosis.
Prostate cancer presents an androgen-dependent growth mediated by the androgen receptor (AR). Androgen pathway blockage is the standard therapy for the treatment of prostate cancer at an advanced stage. In spite of an initial sensitivity, prostate cancer usually becomes refractory to hormone treatment. This resistance can be due to the amplification of the AR gene, AR mutations and the increase in co-activator protein expression. Likewise, growth factors and cytokines can induce AR phosphorylation, independently of ligand fixation. Moreover, there are other AR-independent pathways, such as the acquisition of the neuroendocrine phenotype. In this review, we examine the molecular mechanisms that are involved in the progression of prostate cancer, as well as the ways its cells evade apoptosis.
Assuntos
Animais , Humanos , Masculino , Camundongos , Androgênios , Apoptose , Adenocarcinoma/patologia , Neoplasias Hormônio-Dependentes/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas Reguladoras de Apoptose/fisiologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Terapia de Alvo Molecular , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiologia , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/genética , Receptores Androgênicos/fisiologia , Transdução de SinaisRESUMO
El descubrimiento de los genes BRCA1 y BRCA2 ha llevado a la introducción de pruebas genéticas cada vez más sofisticadas para medir el riesgo de cáncer de mama de origen hereditario, entre otras cosas. En el presente artículo exploramos los criterios a seguir para realizar pruebas para estos genes, así como las implicaciones en el tratamiento para los pacientes en caso de identificarlos.
The discovery of genes BRCA1 and BRCA2 has led to the introduction of genetic tests more complex every time for the evaluation ofthehereditarycancerrisk,amongothers.In the present paper we explore the criteria to decide when to run the testing for the genes, as well as the implications for the treatment of patients who are identified with them.
Assuntos
Feminino , Humanos , Neoplasias da Mama/genética , Genes BRCA1 , Testes Genéticos , Síndromes Neoplásicas Hereditárias/genética , Neoplasias da Mama/classificação , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Comorbidade , Moduladores de Receptor Estrogênico/uso terapêutico , Estrogênios/efeitos adversos , Etnicidade/genética , Saúde da Família , Previsões , Efeito Fundador , Frequência do Gene , Predisposição Genética para Doença/genética , Mastectomia , México/epidemiologia , Neoplasias Hormônio-Dependentes/epidemiologia , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/genética , Síndromes Neoplásicas Hereditárias/epidemiologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , História Reprodutiva , RiscoRESUMO
Epidemiologic studies addressing the association of alcohol consumption with breast cancer consistently suggest a modest association and a dose-response relationship. The epidemiologic evidence does not point to a single mechanism to explain the association, and several mechanisms have been proposed. Alcohol consumption is shown to increase levels of endogenous estrogens, known risk factors for breast cancer. This hypothesis is further supported by data showing that the alcohol-breast cancer association is limited to women with estrogen-receptor positive tumors. Products of alcohol metabolism are known to be toxic and are hypothesized to cause DNA modifications that lead to cancer. Recent research has focused on genes that influence the rate of alcohol metabolism, with genes that raise blood concentrations of acetaldehyde hypothesized to heighten breast cancer risk. Mounting evidence suggests that antioxidant intake(e.g.folate)mayreducealcohol-associatedbreast cancer risk, because it neutralizes reactive oxygen species, a second-stage product of alcohol metabolism. Diets lacking sufficient antioxidant intake, as a result, may further elevate the risk of breast cancer among alcohol consumers. Given that alcohol consumption is increasing worldwide and especially among women in countries of rapid economic growth, a greater understanding of the mechanisms underlying the known alcohol-breast cancer association is warranted.Avoiding overconsumption of alcohol is recommended, especially for women with known risk factors for breast cancer.
Diversos estudios epidemiológicos muestran la asociación del consumo de alcohol con el cáncer de mama de forma consistente, lo que sugiere una modesta asociación, y una relación de dosis-respuesta.La evidencia no apunta a un mecanismo único para explicar la asociación y varios mecanismos han sido propuestos. El consumo de alcohol incrementa los niveles endógenos de estrógeno, un riesgo conocido para cáncer de mama. Esta hipótesis es apoyada por información que muestra que la asociación entre el alcohol y el cáncer de mama está limitada a mujeres con tumores con receptores positivos de estrógeno. Es conocido que los derivados de la metabolización del alcohol son tóxicos, y se ha pensado que causan modificaciones en el DNA que llevan al cáncer. La investigación reciente se ha enfocado en genes que influencian la velocidad con la que se metaboliza el alcohol, y elevan las concentraciones de acetaldehído que se piensa puede aumentar el riesgo de cáncer de mama. La evidencia actual sugiere que la ingesta de antioxidantes (e.g. folato) puede reducirelriesgode cáncer asociadoalalcohol,porque neutraliza las especies reactivas de oxígeno, un producto de la segunda etapa del metabolismo del alcohol. Las dietas con ingesta insuficiente de antioxidantes,como resultado de esto, pueden elevar el riesgo de cáncer entre los consumidores de alcohol.Dado que el consumo de alcohol está incrementando en todo el mundo, especialmente en mujeres de países con rápido crecimiento económico, un mejor entendimiento de los mecanismos subyacentes a la asociación del cáncer de mama y el alcohol es necesario. Evitar el consumo excesivo es recomendado, especialmente para mujeres con factores de riesgo conocidos para cáncer de mama.
Assuntos
Feminino , Humanos , Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias da Mama/epidemiologia , Acetaldeído/efeitos adversos , Acetaldeído/sangue , Antioxidantes , Biotransformação , Neoplasias da Mama/etiologia , Cocarcinogênese , Dano ao DNA , Dieta , Ingestão de Energia , Estrogênios , Etanol/efeitos adversos , Etanol/farmacocinética , Menopausa , México/epidemiologia , Modelos Biológicos , Neoplasias Hormônio-Dependentes/epidemiologia , Neoplasias Hormônio-Dependentes/etiologia , RiscoRESUMO
<p><b>OBJECTIVE</b>To investigate the role of PKD3 in prostate-specific antigen (PSA) expression regulation in androgen-dependent prostate cancer cells and explore the mechanism.</p><p><b>METHODS</b>LNCaP cells containing low level of PKD3 were transfected with pEGFP-C2 or pEGFP-PKD3 plasmid followed by dihydrotestosterone (DHT) treatment, and PSA mRNA level was analyzed by RT-QPCR using 2(-delta delta Ct) method. Wild-type or kinase-dead PKD3 plasmids, human androgen receptor plasmid pSVAR0, pMMTV-luc of AR luciferase reporter and renilla luciferase reporter pRL-SV40 were cotransfected into HEK293 cells, and after treatment with DHT for 24 h, the cells were harvested and AR transcriptional activity were determined by dual-luciferase reporter assay. The subcellular localization of endogenous PKD3 and AR and their colocalization induced by DHT were observed by confocal microscopy.</p><p><b>RESULTS</b>PSA mRNA level triggered by DHT was significantly increased by overexpression of pEGFP-PKD3 in LNCaP cells compared with that in pEGFP-C2 control cells (P<0.001). AR transcription in response to DHT treatment was also significantly up-regulated by wild type PKD3 expression (P<0.001), but partially down-regulated by kinase-dead PKD3 mutant (P<0.01). Endogenous PKD3 and AR in LNCaP cells not only translocated from the cytoplasm to the nucleus, but also colocalized with each other after DHT stimulation.</p><p><b>CONCLUSION</b>Elevated AR transcriptional activity and enhanced expression of PSA induced by PKD3 in response to DHT treatment suggest that PKD3 contributes to the proliferation and malignant growth of androgen-dependent prostate cancer cells.</p>
Assuntos
Humanos , Masculino , Linhagem Celular Tumoral , Neoplasias Hormônio-Dependentes , Metabolismo , Antígeno Prostático Específico , Metabolismo , Neoplasias da Próstata , Metabolismo , Proteína Quinase C , Metabolismo , Ativação Transcricional , Regulação para CimaRESUMO
Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil(R)) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.
Assuntos
Humanos , Masculino , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Células Dendríticas/citologia , Dinoprostona/farmacologia , Fatores Imunológicos/farmacologia , Interferon-alfa/farmacologia , Lipopolissacarídeos/toxicidade , Neoplasias Hormônio-Dependentes/imunologia , Fenótipo , Picibanil/farmacologia , Neoplasias da Próstata/imunologia , Linfócitos T Citotóxicos/imunologiaRESUMO
INTRODUCCIÓN Y OBJETIVOS: La ingesta de sustancias fitoquímicas ha sido investigada con relación a la tumorigénesis, pero los resultados son aún controvertidos. El cáncer es un problema sanitario internacional. El objetivo del presente trabajo fue analizar la asociación entre el consumo de sustancias fitoquímicas y el riesgo de desarrrollar tumores slivales, mamarios y prostáticos. MATERIALES Y MÉTODOS: El esetudio fue de tipo caso -control y participaron 393 personas de ambos sexos, de 15 a 80 años, distribuidos en 127 casos confirmados histológicamente -47 con tumores salivales (TGS), 40 mamarios (TGM), 40 prostáticos (TGP)-y 266 controles pareados por sexo y edad (+5 años), provenientes de los hospitales Privado y Córdoba de la ciudad de Córdoba, y el Sanatorio Adventista de la Plata de la Ciudad de Villa Libertador General San Martín, Entre Riíos, Argentina, durante los años 2004-2009. Luego del consentimiento informado, aprobado por los Comité Institucionales de Ëtica en Investigación en Salud hospitalarios, se completó: historia clínica, cuestionario de frecuencia de consumo alimentario cuali-cuantitativo validado (CFC) y sobre factores de riesgo no nutricionales, referidos a cinco años previos.
Assuntos
Humanos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/síntese química , Neoplasias Hormônio-Dependentes , Neoplasias da Mama/dietoterapia , Neoplasias da Próstata/dietoterapia , Neoplasias das Glândulas Salivares/dietoterapia , Fitoterapia , Fatores de RiscoRESUMO
<p><b>OBJECTIVE</b>To detect HER-2/neu expression in prostate cancer tissues of both androgen dependent and independent groups and to evaluate the role of HER-2/neu in androgen independent prostate cancer.</p><p><b>METHODS</b>Immunohistochemical assay was used in the detection of HER-2/neu in the prostate cancer samples from 30 cases of androgen dependent cancer and 24 cases of androgen independent cancer. The correlation was analyzed between HER-2/neu over-expression and the tumor's clinical stage and Gleason score.</p><p><b>RESULTS</b>The rates of HER-2/neu over-expression were 10% and 33% in the androgen dependent group and the androgen independent group, significantly higher in the Gleason score >7 group and the clinical stage > T2 group than in the -7 group and the > T2 group (14.29% vs. 26.92%, 34.62% vs. 7.14%, P < 0.01).</p><p><b>CONCLUSION</b>The rate of HER-2/neu over-expression is high in androgen independent prostate cancer and is correlated with the tumor stage and Gleason score.</p>
Assuntos
Humanos , Masculino , Androgênios , Fisiologia , Imuno-Histoquímica , Estadiamento de Neoplasias , Neoplasias Hormônio-Dependentes , Metabolismo , Patologia , Neoplasias da Próstata , Metabolismo , Patologia , Receptor ErbB-2RESUMO
<p><b>OBJECTIVE</b>To investigate the effect of dihydrotestosterone (DHT) on the gene transcriptions and expressions of Smad3 and Smad4 in androgen dependent prostate cancer cell line LNCaP, and whether this effect can be suppressed by the androgen receptor inhibitor flutamide.</p><p><b>METHODS</b>The androgen dependent prostate cancer cell line LNCaP was cultured in RPMI 1640 medium and treated with different concentrations of DHT(2, 10, 50 nmol/L) and flutamide (100 nmol/L). Quantitative reverse transcription PCR (RT-PCR) was used to detect the mRNAs of Smad3 and Smad4. The expressions of Smad3 and Smad4 protein were detected by Western blot assay.</p><p><b>RESULTS</b>Compared with the control group without any DHT or flutamide, higher concentration(10, 50 nmol/L) of DHT enhanced the transcription of Smad3 mRNA (P <0.05). Serial concentrations of DHT increased the expression of Smad3 protein(P < 0.05). Flutamide inhibited the up-regulation of both Smad3 mRNA transcription and expression significantly (P <0.05). 10 nmol/L DHT significantly suppressed the transcription of Smad4 (P <0.05). There was considerable suppressions of Smad4 expression at the presence of DHT in different concentrations (P < 0.05). And the degree of this suppression was more significant than that of DHT on Smad4 mRNA transcription. Flutamide inhibited the suppressive effects of DHT on both Smad4 mRNA transcription and expression.</p><p><b>CONCLUSION</b>DHT can enhance the transcription and expression of Smad3, while it decreases the transcription and expression of Smad4 in LNCaP cell line. There is a possible crosstalk between the AR signal and TGF-beta signal passways at the level of Smads.</p>
Assuntos
Humanos , Masculino , Androgênios , Fisiologia , Linhagem Celular Tumoral , Di-Hidrotestosterona , Farmacologia , Flutamida , Farmacologia , Neoplasias Hormônio-Dependentes , Metabolismo , Neoplasias da Próstata , Metabolismo , RNA Mensageiro , Genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Proteína Smad3 , Genética , Proteína Smad4 , Genética , Transcrição GênicaRESUMO
<p><b>OBJECTIVE</b>To explore the apoptosis induction by curcumin in androgen-dependent prostate cancer cell line LNCaP).</p><p><b>METHODS</b>After LNCaP cells were induced by 10, 25, 50, 75, 100 micromol/L curcumin respectively, the cell activity was assayed by MTT at 5, 12 and 24 hours. Flow cytometry and electronic microscopy were adopted to observe cell cycle and morphological changes of LNCaP cells at 24 hours. After 5 hours, the expression of IkappaBalpha in LNCaP cells was detected by Western blotting.</p><p><b>RESULTS</b>The growth of LNCaP cells was suppressed obviously by curcumin in dose-dependent and time-dependent manners in vitro. There were significant differences in inhibition rate among different concentrations and time groups (P < 0.05). Furthermore, curcumin could arrest the cell cycle of LNCaP cells at G2/M phase in a dose-dependent manner (P <0.01). The ratios of apoptosis were significantly higher than those of controls (P < 0. 5). Curcumin could lead to characteristic morphological changes of apoptosis in LNCaP cells after 24 hours. The expression of IkappaBalpha in LNCaP cell did not show marked changes after the exposure to different concentrations of curcumin within 5 hours.</p><p><b>CONCLUSION</b>Curcumin can suppress the growth of LNCaP, and promotes their apoptosis.</p>