Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 22
Filter
1.
Asian Journal of Andrology ; (6): 296-308, 2023.
Article in English | WPRIM | ID: wpr-981952

ABSTRACT

A complete proteomics study characterizing active androgen receptor (AR) complexes in prostate cancer (PCa) cells identified a diversity of protein interactors with tumorigenic annotations, including known RNA splicing factors. Thus, we chose to further investigate the functional role of AR-mediated alternative RNA splicing in PCa disease progression. We selected two AR-interacting RNA splicing factors, Src associated in mitosis of 68 kDa (SAM68) and DEAD (Asp-Glu-Ala-Asp) box helicase 5 (DDX5) to examine their associative roles in AR-dependent alternative RNA splicing. To assess the true physiological role of AR in alternative RNA splicing, we assessed splicing profiles of LNCaP PCa cells using exon microarrays and correlated the results to PCa clinical datasets. As a result, we were able to highlight alternative splicing events of clinical significance. Initial use of exon-mini gene cassettes illustrated hormone-dependent AR-mediated exon-inclusion splicing events with SAM68 or exon-exclusion splicing events with DDX5 overexpression. The physiological significance in PCa was investigated through the application of clinical exon array analysis, where we identified exon-gene sets that were able to delineate aggressive disease progression profiles and predict patient disease-free outcomes independently of pathological clinical criteria. Using a clinical dataset with patients categorized as prostate cancer-specific death (PCSD), these exon gene sets further identified a select group of patients with extremely poor disease-free outcomes. Overall, these results strongly suggest a nonclassical role of AR in mediating robust alternative RNA splicing in PCa. Moreover, AR-mediated alternative spicing contributes to aggressive PCa progression, where we identified a new subtype of lethal PCa defined by AR-dependent alternative splicing.


Subject(s)
Humans , Male , Alternative Splicing , Cell Line, Tumor , DEAD-box RNA Helicases/metabolism , Disease Progression , Gene Expression Regulation, Neoplastic , Prostatic Neoplasms/pathology , Receptors, Androgen/metabolism , RNA Splicing Factors/metabolism
2.
Asian Journal of Andrology ; (6): 287-295, 2023.
Article in English | WPRIM | ID: wpr-981942

ABSTRACT

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.


Subject(s)
Humans , Male , Androgen Antagonists/therapeutic use , Androgens/metabolism , Hepatocyte Nuclear Factor 3-alpha/metabolism , Mutation , Prostatic Neoplasms, Castration-Resistant/drug therapy , Receptors, Androgen/metabolism
3.
Acta Academiae Medicinae Sinicae ; (6): 303-310, 2023.
Article in Chinese | WPRIM | ID: wpr-981268

ABSTRACT

The research on androgen receptor (AR) in breast cancer is advancing.Although the prognostic value of AR in triple negative breast cancer (TNBC) is controversial,a variety of studies have demonstrated that the lack of AR expression exacerbates disease progression.Moreover,the TNBC subtype of AR(-) is more aggressive than that of AR(+) due to the lack of prognostic biomarkers and therapeutic targets.With the discovery and deepening research of novel therapeutic targets such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin and S-phase kinase-associated protein 2 signaling pathways,as well as the emerging of immunotherapies,the treatment options for TNBC are increasing.Regarding the role of AR in TNBC,the studies about the tumor biology of AR(-)TNBC and novel biomarkers for improved management of the disease remain insufficient.In this review,we summarize the research progress of AR in TNBC,put forward avenues for future research on TNBC,and propose potential biomarkers and therapeutic strategies that warrant investigation.


Subject(s)
Humans , Triple Negative Breast Neoplasms/pathology , Receptors, Androgen/metabolism , Prognosis , Biomarkers , Signal Transduction
4.
Journal of Central South University(Medical Sciences) ; (12): 72-78, 2022.
Article in English | WPRIM | ID: wpr-929007

ABSTRACT

OBJECTIVES@#The pathogenesis of androgenetic alopecia (AGA) is related to the level of androgen and its metabolic pathways. The binding of androgen and androgen receptor (AR) depends on the assistance of heat shock protein 27 (HSP27). HSP27 combined with microRNAs (miR)-1 can regulate AR levels. However, it is not clear whether HSP27 and miR-1 jointly participate in the pathogenesis of AGA. This study aims to investigate the role of AR up-regulation in the pathogenesis of AGA and underlying mechanisms.@*METHODS@#A total of 46 male AGA patients (AGA group), who admitted to the First Affiliated Hospital of Guangzhou Medical University from September 2019 to February 2020, and 52 healthy controls admitted to the same period were enrolled in this study. Serum levels of dihydrotestosterone (DHT) and HSP27 in patients and healthy controls were measured by ELISA. Western blotting was used to detect the protein expression of HSP27 and AR in scalp tissues of patients and the healthy controls. The levels of HSP27, AR, and miR-1 were analyzed using real-time PCR. Human dermal papilla cells were transfected with HSP27 siRNA to inhibit the expression of HSP27. MiR-1 and miR-1 inhibitors were transfected simultaneously or separately into cells and then the changes in AR protein expression were detected.@*RESULTS@#The levels of DHT and HSP27 in the AGA group were (361.4±187.7) pg/mL and (89.4±21.8) ng/mL, respectively, which were higher than those in the control group [(281.8±176.6) pg/mL and (41.2±13.7) ng/mL, both P<0.05]. However, there was no significant difference in serum HSP27 and AR levels among AGA patients with different degrees of hair loss (P>0.05). Correlation analysis showed that there was a positive correlation between HSP27 level and DHT level in the AGA patients (P<0.05). The level of HSP27 mRNA in scalp tissue was negatively correlated with that of miR-1 mRNA (P<0.05). Compared with the control group, the levels of HSP27 protein, AR protein, HSP27 mRNA, and AR mRNA in scalp tissues of AGA group were significantly increased (P<0.05). The up-regulation of HSP27 in scalp tissues of AGA patients was closely related to the increased levels of AR. However, the level of miR-1 in scalp tissues of AGA patients was significantly down-regulated, contrary to the expression of AR (P<0.05). Further in cell studies showed that inhibition of HSP27 or miR-1 expression in human dermal papilla cells could inhibit the expression of AR, and inhibition of both HSP27 and miR-1 expression was found to have an accumulative effect on AR, with statistically significant differences (all P<0.05).@*CONCLUSIONS@#HSP27 could combine with miR-1 to up-regulate AR levels, which is closely related to the development of AGA.


Subject(s)
Humans , Male , Alopecia/pathology , HSP27 Heat-Shock Proteins/metabolism , MicroRNAs/genetics , RNA, Messenger , Receptors, Androgen/metabolism , Up-Regulation
5.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 518-526, 2022.
Article in English | WPRIM | ID: wpr-939916

ABSTRACT

Benign prostatic hyperplasia (BPH) is a chronic male disease characterized by the enlarged prostate. Celtis chosenianaNakai (C. choseniana) is medicinally used to alleviate pain, gastric disease, and lung abscess. In this study, the effect of C. choseniana extract on BPH was investigated using testosterone-induced rats. Sprague Dawley rats were divided into five groups: control, BPH (testosterone 5 mg·kg-1), Fina (finasteride 2 mg·kg-1), and C. choseniana (50 and 100 mg·kg-1). After four weeks of TP treatment with finasteride or C. choseniana, prostate weights and DHT levels were measured. In addition, the prostates were histopathologically examined and measured for protein kinase B (Akt)/nuclear factor-κB (NF-κB)/AR signaling, proliferation, apoptosis, and autophagy. Prostate weight and epithelial thickness were reduced in the C. choseniana groups compared with that in the BPH group. The extract of C. choseniana acted as a 5α reductase inhibitor, reducing DHT levels in the prostate. Furthermore, the extract of C. choseniana blocked the activation of p-Akt, nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH. Moreover, the expression of Bax, PARP-1, and p53 increased, while the expression of bcl-2 decreased. The present study demonstrated that C. choseniana extract alleviated testosterone-induced BPH by suppressing 5α reductase and Akt/NF-κB activation, reducing AR signaling and inducing apoptosis and autophagy in the prostate. These results suggested that C. choseniana probably contain potential herbal agents to alleviate BPH.


Subject(s)
Animals , Male , Rats , Cholestenone 5 alpha-Reductase/metabolism , Finasteride/adverse effects , NF-kappa B/genetics , Plant Extracts/therapeutic use , Prostatic Hyperplasia/drug therapy , Proto-Oncogene Proteins c-akt/genetics , Rats, Sprague-Dawley , Receptors, Androgen/metabolism , Testosterone , Ulmaceae/metabolism
6.
Protein & Cell ; (12): 29-38, 2021.
Article in English | WPRIM | ID: wpr-880916

ABSTRACT

Prostate cancer is the most commonly diagnosed non-cutaneous cancers in North American men. While androgen deprivation has remained as the cornerstone of prostate cancer treatment, resistance ensues leading to lethal disease. Forkhead box A1 (FOXA1) encodes a pioneer factor that induces open chromatin conformation to allow the binding of other transcription factors. Through direct interactions with the Androgen Receptor (AR), FOXA1 helps to shape AR signaling that drives the growth and survival of normal prostate and prostate cancer cells. FOXA1 also possesses an AR-independent role of regulating epithelial-to-mesenchymal transition (EMT). In prostate cancer, mutations converge onto the coding sequence and cis-regulatory elements (CREs) of FOXA1, leading to functional alterations. In addition, FOXA1 activity in prostate cancer can be modulated post-translationally through various mechanisms such as LSD1-mediated protein demethylation. In this review, we describe the latest discoveries related to the function and regulation of FOXA1 in prostate cancer, pointing to their relevance to guide future clinical interventions.


Subject(s)
Humans , Male , Amino Acid Sequence , Epigenesis, Genetic , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Hepatocyte Nuclear Factor 3-alpha/metabolism , Histone Demethylases/metabolism , Histones/metabolism , Mutation , Prostate/pathology , Prostatic Neoplasms/pathology , Protein Binding , Protein Processing, Post-Translational , Receptors, Androgen/metabolism , Signal Transduction , Transcription, Genetic
7.
Biol. Res ; 54: 3-3, 2021. graf, ilus
Article in English | LILACS | ID: biblio-1505792

ABSTRACT

BACKGROUND: Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake­via AMP-activated protein kinase (AMPK)­after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). METHODS: Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of ß-myosin heavy chain (ß-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). RESULTS: Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated ß-mhc, Hk2 and Pfk2 mRNA levels. CONCLUSION: These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.


Subject(s)
Animals , Male , Rats , Testosterone/pharmacology , Receptors, Androgen/metabolism , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , AMP-Activated Protein Kinases/metabolism , Glucose/metabolism , Signal Transduction , Cells, Cultured , Hypertrophy , Myocardium/pathology
8.
Asian Journal of Andrology ; (6): 539-544, 2018.
Article in English | WPRIM | ID: wpr-1009639

ABSTRACT

The epithelium of the human epididymis maintains an appropriate luminal environment for sperm maturation that is essential for male fertility. Regional expression of small noncoding RNAs such as microRNAs contributes to segment-specific gene expression and differentiated functions. MicroRNA profiles were reported in human epididymal tissues but not specifically in the epithelial cells derived from those regions. Here, we reveal miRNA signatures of primary cultures of caput, corpus, and cauda epididymis epithelial cells and of the tissues from which they were derived. We identify 324 epithelial cell-derived microRNAs and 259 tissue-derived microRNAs in the epididymis, some of which displayed regionalized expression patterns in cells and/or tissues. Caput cell-enriched miRNAs included miR-573 and miR-155. Cauda cell-enriched miRNAs included miR-1204 and miR-770. Next, we determined the gene ontology pathways associated with in silico predicted target genes of the differentially expressed miRNAs. The effect of androgen receptor stimulation on miRNA expression was also investigated. These data show novel epithelial cell-derived miRNAs that may regulate the expression of important gene networks that are responsible for the regionalized gene expression and function of the epididymis.


Subject(s)
Adult , Humans , Male , Androgens/pharmacology , Computer Simulation , Epididymis/metabolism , Epithelial Cells/metabolism , Epithelium/metabolism , Gene Expression Profiling , Gene Regulatory Networks/drug effects , MicroRNAs/genetics , Primary Cell Culture , Receptors, Androgen/metabolism , Sequence Analysis, RNA
9.
Asian Journal of Andrology ; (6): 511-517, 2018.
Article in English | WPRIM | ID: wpr-1009623

ABSTRACT

We sought to investigate the underlying mechanism of action of the long noncoding RNA (lncRNA) LOC283070 in the development of androgen independence in prostate cancer. The interactions between LOC283070 and target proteins were investigated by RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays. Subcellular fractionation and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the subcellular localization of LOC283070. Western blotting was performed to detect the expression of prohibitin 2 (PHB2). Luciferase activity assays were performed to evaluate the effects of LOC283070 and PHB2 on the androgen receptor (AR) signaling pathway. A methyl thiazolyl tetrazolium (MTT) assay and a growth curve assay were used to test cell viability. Flow cytometry was performed to analyze cell cycles. A transwell assay was employed to test cell migration. We identified PHB2 as an interaction partner of LOC283070 in the pull-down and RIP experiments. Furthermore, we confirmed that the enrichment of LOC283070 with PHB2 in androgen-independent LNCaP (LNCaP-AI) cells was much greater than that in LNCaP cells. Moreover, the expression of PHB2 was not significantly different between the two cell lines, and the expression of LOC283070 in the nuclei of the LNCaP-AI cells was significantly greater than that in the LNCaP cells. In vitro data revealed that PHB2 overexpression significantly inhibited AR activity and cell proliferation and migration and induced accumulation of prostate cancer cells in G0/G1 phase. Moreover, the overexpression of LOC283070 fully abrogated the effects of PHB2 overexpression. In conclusion, we found that LOC283070 can bind to PHB2 located in the nucleus and inhibit its effect, and this is one of the mechanisms by which LOC283070 is involved in the transition of LNCaP cells into androgen-independent cells.


Subject(s)
Humans , Male , Androgens/metabolism , Cell Line, Tumor , Cell Proliferation/physiology , Gene Expression Regulation, Neoplastic , Prohibitins , Prostatic Neoplasms/metabolism , RNA, Long Noncoding/metabolism , Receptors, Androgen/metabolism , Repressor Proteins/metabolism , Signal Transduction/physiology
10.
Asian Journal of Andrology ; (6): 276-283, 2018.
Article in English | WPRIM | ID: wpr-1009560

ABSTRACT

Androgen deprivation in men leads to increased adiposity, but the mechanisms underlying androgen regulation of fat mass have not been fully defined. Androgen receptor (AR) is expressed in monocytes/macrophages, which are resident in key metabolic tissues and influence energy metabolism in surrounding cells. Male mice bearing a cell-specific knockout of the AR in monocytes/macrophages (M-ARKO) were generated to determine whether selective loss of androgen signaling in these cells would lead to altered body composition. Wild-type (WT) and M-ARKO mice (12-22 weeks of age, n = 12 per group) were maintained on a regular chow diet for 8 weeks and then switched to a high-fat diet for 8 additional weeks. At baseline and on both the regular chow and high-fat diets, no differences in lean mass or fat mass were observed between groups. Consistent with the absence of differential body weight or adiposity, no differences in food intake (3.0 ± 0.5 g per day for WT mice vs 2.8 ± 0.4 g per day for M-ARKO mice) or total energy expenditure (0.6 ± 0.1 Kcal h-1 for WT mice vs 0.5 ± 0.1 Kcal h-1 for M-ARKO mice) were evident between groups during high-fat feeding. Liver weight was greater in M-ARKO than that in WT mice (1.5 ± 0.1 g vs 1.3 ± 0.0 g, respectively, P = 0.02). Finally, M-ARKO mice did not exhibit impairments in glucose tolerance or insulin sensitivity relative to WT mice at any study time point. In aggregate, these findings suggest that AR signaling specifically in monocytes/macrophages does not contribute to the regulation of systemic energy balance, adiposity, or insulin sensitivity in male mice.


Subject(s)
Animals , Male , Mice , Adiposity/genetics , Blood Glucose/metabolism , Energy Metabolism/genetics , Glucose Tolerance Test , Homeostasis/genetics , Liver/anatomy & histology , Macrophages/metabolism , Mice, Knockout , Monocytes/metabolism , Organ Size , Receptors, Androgen/metabolism , Signal Transduction
11.
Biol. Res ; 50: 10, 2017. graf
Article in English | LILACS | ID: biblio-838959

ABSTRACT

BACKGROUND: The muskrat is a seasonal breeder. Males secrete musk to attract females during the breeding season. The testosterone binding to the androgen receptor (AR) in musk glands of muskrat may play an important role conducting the musk secretion process. METHODS: The musk gland, testis and blood samples of musk rats are collected in both breeding and non-breeding seasons. Some part of the samples are kept in liquid nitrogen for transcriptome analysis and Western blotting test. Some part of the samples are kept in 70% alcohol for histology experiment, blood samples are kept at -20 °C for the serum testosterone measurement experiment. RESULTS: This study demonstrates that the quantity of secreted musk, the volume of the musk glands, the diameter of the gland cells and AR expression are all higher during the breeding season than at other times (p < 0.01). StAR, P450scc and 3ß-HSD expression in the Leydig cells of the testis were also higher during this season, as was serum testosterone. AR was also observed in the gland cells of two other musk-secreting animals, the musk deer and small Indian civet, in their musk glands. These results suggest that the testes and musk glands co-develop seasonally. CONCLUSION: The musk glands' seasonal development and musk secretion are regulated by the testes, and testosterone plays an important role in the seasonal development of musk glands.


Subject(s)
Animals , Male , Scent Glands/growth & development , Scent Glands/metabolism , Testis/metabolism , Fatty Acids, Monounsaturated/metabolism , Organ Size , Reference Values , Reproduction/physiology , Scent Glands/anatomy & histology , Seasons , Testis/growth & development , Testosterone/blood , Breeding , Enzyme-Linked Immunosorbent Assay , Fatty Acids, Monounsaturated/analysis , Immunohistochemistry , Receptors, Androgen/analysis , Receptors, Androgen/metabolism , Blotting, Western , Arvicolinae , Sequence Analysis, RNA , Leydig Cells/metabolism
12.
Rev. latinoam. enferm ; 23(2): 352-360, Feb-Apr/2015. tab, graf
Article in English | LILACS, BDENF | ID: lil-747162

ABSTRACT

OBJECTIVE: to analyze the scientific literature on home-based family care of people with severe mental illness. METHOD: integrative review of 14 databases (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, EMI, ISOC, JBI COnNECT, LILACS, PsycINFO, PubMed, SciELO, and Scopus) searched with the key words "family caregivers", "severe mental illness", and "home" between 2003 and 2013. RESULTS: of 787 articles retrieved, only 85 met the inclusion criteria. The articles appeared in 61 journals from different areas and disciplines, mainly from nursing (36%). The countries producing the most scientific literature on nursing were Brazil, the UK, and the US, and authorship predominantly belonged to university centers. A total of 54.12% of the studies presented quantitative designs, with descriptive ones standing out. Work overload, subjective perspectives, and resources were the main topics of these papers. CONCLUSIONS: the international scientific literature on home-based, informal family care of people with severe mental disorder is limited. Nursing research stands out in this field. The prevalent topics coincide with the evolution of the mental health system. The expansion of the scientific approach to family care is promoted to create evidence-based guidelines for family caregivers and for the clinical practice of professional caregivers. .


OBJETIVO: analisar a produção científica sobre o cuidado familiar de pessoas com transtorno mental grave em casa. MÉTODO: revisão integrativa de 14 bases de dados (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, EMI, ISOC, JBI Connect, LILACS, PsycInfo e PubMed, SciELO, e Scopus), com as palavras-chave "cuidadores familiares", "TMG" (transtornos mentais graves ) e "casa", realizada entre 2003 e 2013. RESULTADOS: dos 787 artigos retornados, somente 85 atenderam os critérios de inclusão. Os artigos vieram de 61 periódicos de diferentes áreas e disciplinas, principalmente de enfermagem (36%). Os países com maior produção científica sobre enfermagem foram o Brasil, o Reino Unido e os Estados Unidos, e a autoria era predominantemente de centros universitários. Um total de 54,12% dos estudos apresentou delineamento quantitativo, e os descritivos se destacaram. Os principais temas desses trabalhos foram sobrecarga de trabalho, perspectivas subjetivas e recursos. CONCLUSÕES: a produção cientifica internacional sobre o cuidado familiar informal de pessoas com doenças mentais graves em casa é limitada. A pesquisa em enfermagem se destaca nesse campo. Os temas prevalentes coincidem com a evolução do sistema de saúde mental. Estimula-se a expansão da abordagem científica do cuidado familiar de modo a encontrar evidências para criar guias para cuidadores familiares e para a prática clínica de cuidadores profissionais. .


OBJETIVO: analizar la producción científica sobre el cuidado familiar de la persona con trastorno mental grave en el hogar familiar. MÉTODO: revisión integradora en 14 bases de datos (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, IME, ISOC, JBI ConNECT, LILACS, PsycInfo, PubMed, SciELO y Scopus), con las palabras clave "cuidadores familiares", "TMG" y "hogar"; realizada entre 2003 y 2013. RESULTADOS: de 787 artículos recuperados, sólo 85 cumplieron con los criterios de inclusión. Los artículos procedieron de 61 revistas de diferentes áreas y disciplinas destacando la disciplina de enfermería (36%). Los países con mayor producción científica sobre enfermería fueron Brasil, Reino Unido y EEUU. En la autoría predominaron los centros universitarios. El 54,12% de los estudios presentó diseño cuantitativo, sobresaliendo los descriptivos. Las temáticas destacadas fueron sobrecarga, perspectivas subjetivas y recursos. CONCLUSIONES: la producción científica internacional sobre el cuidado informal familiar de la persona con trastorno mental grave, en el contexto del hogar familiar, es limitada. En este campo, destaca la investigación de enfermería. Las temáticas prevalentes coinciden con la evolución del sistema de salud mental. Se estimula la ampliación del abordaje científico del cuidado familiar con el fin de encontrar evidencias para la elaboración de guías de cuidadores familiares y para la práctica clínica de cuidadores profesionales. .


Subject(s)
Humans , Female , Adipogenesis , Adipocytes/metabolism , Adult Stem Cells/physiology , Androgens/physiology , Dihydrotestosterone/pharmacology , Testosterone/physiology , Androgen Antagonists/pharmacology , Androgens/pharmacology , /metabolism , CCAAT-Enhancer-Binding Protein-beta/genetics , CCAAT-Enhancer-Binding Protein-beta/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , Cells, Cultured , Flutamide/pharmacology , Gene Expression , Lipid Metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , Receptors, Androgen/metabolism , Signal Transduction , Testosterone/pharmacology
13.
Yonsei Medical Journal ; : 16-23, 2015.
Article in English | WPRIM | ID: wpr-201315

ABSTRACT

PURPOSE: To investigate the effects of anthocyanins extracted from black soybean, which have antioxidant activity, on apoptosis in vitro (in hormone refractory prostate cancer cells) and on tumor growth in vivo (in athymic nude mouse xenograft model). MATERIALS AND METHODS: The growth and viability of DU-145 cells treated with anthocyanins were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis was assessed by DNA laddering. Immunoblotting was conducted to evaluate differences in the expressions of p53, Bax, Bcl, androgen receptor (AR), and prostate specific antigen (PSA). To study the inhibitory effects of anthocyanins on tumor growth in vivo, DU-145 tumor xenografts were established in athymic nude mice. The anthocyanin group was treated with daily oral anthocyanin (8 mg/kg) for 14 weeks. After 2 weeks of treatment, DU-145 cells (2x106) were inoculated subcutaneously into the right flank to establish tumor xenografts. Tumor dimensions were measured twice a week using calipers and volumes were calculated. RESULTS: Anthocyanin treatment of DU-145 cells resulted in 1) significant increase in apoptosis in a dose-dependent manner, 2) significant decrease in p53 and Bcl-2 expressions (with increased Bax expression), and 3) significant decrease in PSA and AR expressions. In the xenograft model, anthocyanin treatment significantly inhibit tumor growth. CONCLUSION: This study suggests that anthocyanins from black soybean inhibit the progression of prostate cancer in vitro and in a xenograft model.


Subject(s)
Animals , Humans , Male , Anthocyanins/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Mice, Inbred C57BL , Mice, Nude , NAD/metabolism , Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/genetics , Receptors, Androgen/metabolism , Tumor Suppressor Protein p53/metabolism , Xenograft Model Antitumor Assays , bcl-2-Associated X Protein/genetics
14.
Braz. j. phys. ther. (Impr.) ; 18(6): 513-520, 09/01/2015. graf
Article in English | LILACS | ID: lil-732354

ABSTRACT

BACKGROUND: Knowing the potential for and limitations of information generated using different evaluation instruments favors the development of more accurate functional diagnoses and therapeutic decision-making. OBJECTIVE: To investigate the relationship between the number of compensatory movements when climbing up and going down stairs, age, functional classification and time taken to perform a tested activity (TA) of going up and down stairs in boys with Duchenne muscular dystrophy (DMD). METHOD: A bank of movies featuring 30 boys with DMD performing functional activities was evaluated. Compensatory movements were assessed using the climbing up and going down stairs domain of the Functional Evaluation Scale for Duchenne Muscular Dystrophy (FES-DMD); age in years; functional classification using the Vignos Scale (VS), and TA using a timer. Statistical analyses were performed using the Spearman correlation test. RESULTS: There is a moderate relationship between the climbing up stairs domain of the FES-DMD and age (r=0.53, p=0.004) and strong relationships with VS (r=0.72, p=0.001) and TA for this task (r=0.83, p<0.001). There were weak relationships between the going down stairs domain of the FES-DMD-going down stairs with age (r=0.40, p=0.032), VS (r=0.65, p=0.002) and TA for this task (r=0.40, p=0.034). CONCLUSION: These findings indicate that the evaluation of compensatory movements used when climbing up stairs can provide more relevant information about the evolution of the disease, although the activity of going down stairs should be investigated, with the aim of enriching guidance and strengthening accident prevention. Data from the FES-DMD, age, VS and TA can be used in a complementary way to formulate functional diagnoses. Longitudinal studies and with broader age groups may supplement this information. .


CONTEXTUALIZAÇÃO: Conhecer as potencialidades e limitações das informações geradas por diferentes instrumentos de avaliação favorece o desenvolvimento mais preciso do diagnóstico funcional e da tomada de decisão terapêutica. OBJETIVO : Investigar a relação entre o número de movimentos compensatórios ao subir e descer escadas, idade, classificação funcional e tempo de realização de atividade (TA) em meninos com Distrofia Muscular de Duchenne (DMD). MÉTODO : Foi utilizado banco de filmes de 30 meninos com DMD realizando atividades funcionais. Os movimentos compensatórios foram avaliados pela Escala de Avaliação Funcional para Distrofia Muscular de Duchenne (FES-DMD), domínio subir e descer escada; a idade, mensurada em anos; a classificação funcional foi pesquisada pela Escala de Vignos (EV), e o TA foi cronometrado. Foi utilizado o teste de correlação de Spearman. RESULTADOS : Existe moderada relação entre a FES-DMD-subir escada e a idade (r=0,53, p=0,004) e forte relação com a EV (r=0,72, p=0,001) e TA dessa tarefa (r=0,83, p<0,001). Houve fraca relação entre a FES-DMD-descer escada e a idade (r=0,40, p=0,032), EV (r=0,65, p=0,002) e o TA dessa tarefa (r=0,40, p=0,034). CONCLUSÃO : Esses achados indicam que a avaliação da tarefa de subir escada pode trazer informações mais relevantes sobre a evolução da doença, embora a atividade de descer escada deva ser pesquisada visando à orientação e prevenção de acidentes. A utilização conjunta de dados provenientes da FES-DMD, da idade e do TA pode se complementar para formulação do diagnóstico funcional. Estudos longitudinais e com outras faixas etárias mais amplas podem complementar tal informação. .


Subject(s)
Humans , Male , Prostatic Hyperplasia/metabolism , Receptors, Androgen/metabolism , Binding, Competitive , Buffers , Charcoal , Cytosol/metabolism , Dextrans , Dihydrotestosterone/metabolism , Electrophoresis, Agar Gel , Enzyme Activation/drug effects , Estrenes/metabolism , Metribolone , Molybdenum/pharmacology , Progesterone/metabolism , Protease Inhibitors/pharmacology , Temperature , Tartrates/pharmacology , Testosterone Congeners/metabolism
15.
Yonsei Medical Journal ; : 1214-1221, 2014.
Article in English | WPRIM | ID: wpr-210341

ABSTRACT

PURPOSE: We investigated sex-hormone receptor expression as predicting factor of recurrence and progression in patients with non-muscle invasive bladder cancer. MATERIALS AND METHODS: We retrospectively evaluated tumor specimens from patients treated for transitional cell carcinoma of the bladder at our institution between January 2006 and January 2011. Performing immunohistochemistry using a monoclonal androgen receptor antibody and monoclonal estrogen receptor-beta antibody on paraffin-embedded tissue sections, we assessed the relationship of immunohistochemistry results and prognostic factors such as recurrence and progression. RESULTS: A total of 169 patients with bladder cancer were evaluated in this study. Sixty-threepatients had expressed androgen receptors and 52 patients had estrogen receptor beta. On univariable analysis, androgen receptor expression was significant lower in recurrence rates (p=0.001), and estrogen receptor beta expression was significant higher in progression rates (p=0.004). On multivariable analysis, significant association was found between androgen receptor expression and lower recurrence rates (hazard ratio=0.500; 95% confidence interval, 0.294 to 0.852; p=0.011), but estrogen receptor beta expression was not significantly associated with progression rates. CONCLUSION: We concluded that the possibility of recurrence was low when the androgen receptor was expressed in the bladder cancer specimen and it could be the predicting factor of the stage, number of tumors, carcinoma in situ lesion and recurrence.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Carcinoma, Transitional Cell/metabolism , Disease Progression , Disease-Free Survival , Multivariate Analysis , Neoplasm Invasiveness , Prognosis , Receptors, Androgen/metabolism , Receptors, Estrogen/metabolism , Retrospective Studies , Risk Factors , Biomarkers, Tumor/metabolism , Urinary Bladder Neoplasms/metabolism
16.
Int. braz. j. urol ; 39(6): 875-883, Nov-Dec/2013. tab, graf
Article in English | LILACS | ID: lil-699121

ABSTRACT

Objectives Five-alpha reductase inhibitors (5ARIs) are known as chemopreventive agents in prostate cancer with a risk of high-grade disease. This study evaluated the effects of 5ARI on androgen receptor (AR) and proteins involved in prostate cell growth such as HOXB13 expression in human prostate tissue and LNCaP prostate cancer cells. Materials and Methods We retrospectively selected 21 patients who underwent TURP between March 2007 and February 2010 for previously confirmed BPH by prostate biopsy. They were grouped into control (group 1, n = 9) and 5ARI treatment (group 2, n = 12) before TURP. AR and HOXB13 expression in prostate tissue was evaluated by immunohistochemical staining. We tested the effect of 5ARI on the expression of AR, prostate specific antigen (PSA) and HOXB13 in LNCaP cells. Cells were assessed by Western blot analysis, MTT in vitro proliferation assay, and ELISA. Results: Group 2 showed stronger reactivity for AR and HOXB13 than those of the group 1. MTT assay showed death of LNCaP cells at 25uM of 5ARI. At the same time, ELISA assay for PSA showed that 5ARI inhibited secretion of PSA in LNCaP cells. Western blot analysis showed that 5ARI did not greatly alter AR expression but it stimulated the expression of HOXB13. Conclusions These results demonstrated that 5ARI influences AR and HOXB13 expression in both LNCaP cells and human prostate tissue. In order to use 5ARI in chemoprevention of prostate cancer, we still need to clarify the influence of 5ARI in ARs and oncogenic proteins and its regulation pathway. .


Subject(s)
Aged , Humans , Male , /therapeutic use , Homeodomain Proteins/metabolism , Prostatic Hyperplasia/drug therapy , Receptors, Androgen/metabolism , Azasteroids/therapeutic use , Blotting, Western , Cell Line, Tumor , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Prostate-Specific Antigen/blood , Prostate/chemistry , Prostate/drug effects , Prostatic Hyperplasia/metabolism , Retrospective Studies , Time Factors , Tumor Cells, Cultured , Transcription Factors/analysis
17.
Braz. j. med. biol. res ; 44(11): 1118-1124, Nov. 2011. ilus
Article in English | LILACS | ID: lil-604270

ABSTRACT

The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol.


Subject(s)
Animals , Male , Mice , Aging/metabolism , Cellular Senescence/physiology , Estradiol/metabolism , Myocytes, Cardiac/physiology , Receptors, Androgen/metabolism , Testosterone/pharmacology , Aging/pathology , Biomarkers/analysis , /drug effects , Models, Animal , Orchiectomy , Random Allocation , Retinoblastoma Protein/metabolism , Telomere Shortening/drug effects , Testosterone/deficiency , /metabolism
18.
Yonsei Medical Journal ; : 843-850, 2008.
Article in English | WPRIM | ID: wpr-153691

ABSTRACT

PURPOSE: Exposure of male reproductive organs to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) has been reported to cause developmental changes. In this study, we evaluated the effects of in utero TCDD exposure on male reproductive development. MATERIALS AND METHODS: Pregnant C57BL/6 mice were administered a single intraperitoneal injection of TCDD (1microgram/kg) on gestation day (GD) 15. The offspring were examined in the immature stage on postnatal day (PND) 30 and in the mature stage on PND 60. The testes were examined for histological changes, androgen receptor (AR), proliferating cell nuclear antigen (PCNA) and apoptosis following the measurement of morphological changes. RESULTS: Anogenital distance (AGD) and testis weights were reduced by TCDD exposure both on PND 30 and PND 60 while body weights and length of male offspring were not affected by TCDD. The regular sperm developmental stage was impaired with TCDD treatment on PND 30. However, no difference was found between the control group and TCDD groups on PND 60. Simultaneously, the expression of AR was also reduced on PND 30, while it was increased on PND 60 compared with the control group. The expression of PCNA was decreased whereas apoptosis was not affected by TCDD both on PND 30 and PND 60. CONCLUSION: These results suggest that in utero exposure to TCDD influences the development of testes by inhibiting the expression of AR and PCNA. Moreover, the adverse effects of TCDD on male offspring reduced over time.


Subject(s)
Animals , Female , Male , Mice , Pregnancy , Apoptosis/drug effects , Cell Proliferation , Embryonic Development/drug effects , Environmental Pollutants/toxicity , Maternal Exposure , Mice, Inbred C57BL , Organ Size/drug effects , Receptors, Androgen/metabolism , Testis/drug effects , Polychlorinated Dibenzodioxins/toxicity
19.
Int. j. morphol ; 25(3): 579-585, Sept. 2007. ilus, tab
Article in English | LILACS | ID: lil-626907

ABSTRACT

The vomeronasal organ (VNO) is a tubular chemoreceptory organ which detects environmental pheromones and is essential for mammalian normal reproductive activity. A sensitive chemoreceptory neuroepithelium lines the concave VNO wall and the opposite, convex wall is lined by a seudostratified, receptor-free epithelium. The secretion of the Jacobson glands (JG) -tubuloacinary glands lying in the lamina propia of the VNO - is essential for pheromones contacting vomeronasal organ chemoreceptors. Tubuloacinary glands lying in the connective tissue of the nasal septum mucosa (Bowman glands), can be classified as ventral and dorsal, according to their location. Positivity to PAS and Alcyan blue reactions and androgen receptor immunolocalization was evaluated with a semiquantitative system (0,1, 2 or 3 crosses) in JG, ventral Bowman glands (VBG), dorsal Bowman glands (DBG), sensitive chemoreceptory neuroepithelium (Ne), receptor-free epithelium (RFE) and nasal septum respiratory epithelium (RE) histological slides of male rats at 5, 15, 25 and 35 days of age. The VBG and JG were intensely positive to PAS reaction since 5 days of age, and weakly positive to Alcyan blue reaction (AB) since 15 days of age, but not at 5 days of age. Both JG and VBG were strongly positive to androgen receptor immunolocalization at all ages studied (15, 25 and 35 days of age). DBG were always negative to both PAS and AB reactions. The NE and the RFE and nasal mucosa luminar epithelium were negative. To our knowledge, this is the first report of androgen receptor (AR) immunolocalization in the vomeronasal organ and the nasal septum mucosa. The present results also suggest an influence of androgens on the mechanism of pheromones contacting with the Ne of the VNO through regulation of the Jacobson glands secretion.


El órgano vomeronasal (VNO) es un órgano quimioreceptor, tubular, que detecta feromonas ambientales. Es esencial para la actividad reproductiva normal de los mamíferos. El VNO está formado por un neuroepitelio quimiosensible (pared cóncava, Ne) y un epitelio pseudoestratificado (epitelio libre de receptores: RFE) en la pared opuesta, convexa. La secreción de las glándulas tubuloacinares de Jacobson (JG), ubicadas en la lámina propia del VNO, son esenciales para que las feromonas entren en contacto con el Ne. Las glándulas tubuloacinares ubicadas en la mucosa del tabique nasal (glándulas del Bowman), se pueden clasificar como ventrales (VBG) y dorsales (DBG), según su localization. La positividad a las técnicas de PAS, Azul de Alcián (AB) e immunolocalization del receptor de andrógeno (AR), fueron evaluadas con un sistema semicuantitativo (0, 1, 2 o 3 cruces) en láminas histológicas de JG, VBG, DBG, Ne, RFE y del epitelio del tabique nasal (RE) en ratas macho de 5, 15, 25 y 35 días de edad. Las VBG y JG fueron intensamente positivas a la reacción de PAS desde los 5 días de edad y débilmente positivas a la reacción de AB desde los 15 días de edad, pero no a los 5 días de la edad. Las JG y VBG fueron fuertemente positivas a la immunolocalization del AR en las edades estudiadas (15, 25 y 35 días de edad). Las DBG fueron siempre negativas a las reacciones de PAS y AB. El NE, el RFE y el RE fueron negativos. Según nuestro conocimiento, éste es el primer informe de immunolocalization del AR en el VNO y la mucosa del tabique nasal. Los actuales resultados sugieren una influencia de los andrógenos en el mecanismo por el cual entran en contacto las feromonas y el Ne, a través de la regulación por andrógenos de la secreción de las JG.


Subject(s)
Animals , Rats , Vomeronasal Organ/metabolism , Periodic Acid-Schiff Reaction , Immunohistochemistry , Receptors, Androgen/metabolism , Rats, Sprague-Dawley , Vomeronasal Organ/growth & development , Alcian Blue
20.
Yonsei Medical Journal ; : 811-816, 2006.
Article in English | WPRIM | ID: wpr-169432

ABSTRACT

Expression of estrogen receptors (ER)-alpha and -beta, as well as androgen receptor (AR), in hepatocellular carcinoma (HCC) is thought to be correlated with prognosis, survival, and male prevalence of HCC. These hypotheses are based on investigations of European patients; however the expression patterns of these receptors in Asian patients are largely unknown. In this study, we collected liver carcinoma and peritumor tissues from 32 patients (9 females and 23 males) in South Korea. The expression of ERs and ARs was studied using RT-PCR. Wild-type ER-alpha and AR were expressed in all of the samples investigated, and their expression was independent of the causal virus or patient sex. Expression of the ER-alpha variant was independent of sex (100% female vs. 91.3% male) and HCV and HBV status (91.3% vs. 100%). Wild-type ER-beta was expressed more often in HCV patients than in HBV patients (95.7% vs. 44.4%; p < 0.05). In conclusion, the stronger ER-alpha variant expression in HCC tissues implies that this variant has an important role in HCC development. However, at least in Korean patients, expression of the ER-alpha variant (vER-alpha) is not related to male HCC prevalence. In addition, the predominant expression of ER-beta in HCV patients suggests that it plays an important role in HCV-induced liver disease.


Subject(s)
Middle Aged , Male , Humans , Female , Aged , Sex Factors , Receptors, Estrogen/metabolism , Receptors, Androgen/metabolism , Liver Neoplasms/ethnology , Korea , Hepatitis B virus/isolation & purification , Hepacivirus/isolation & purification , Carcinoma, Hepatocellular/ethnology , Biomarkers/metabolism , Asian People
SELECTION OF CITATIONS
SEARCH DETAIL