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2.
Chemosphere ; 235: 713-718, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31279121

RESUMO

Chemical leukoderma is a patchy hypopigmentation in the skin. Phenol derivatives such as raspberry ketone have been reported to cause the development of occupationally induced leukoderma. Recently, 2% (w/w) rhododenol, a reduced form of raspberry ketone used in a skin-lightning agent, also caused the development of leukoderma in >16,000 users, about 2% of all users, in Asian countries including Japan. However, a method for assessing the risk of leukoderma caused by 2% rhododenol has not been established despite the fact that the development of leukoderma caused by 30% rhododenol was previously shown in animal experiments. Establishment of a novel technique for risk assessment of leukoderma in humans caused by external treatment with chemicals is needed to prevent a possible future chemical disaster. This study demonstrated that external treatment with 2% rhododenol and the same concentration of raspberry ketone caused the development of leukoderma in murine tail skin without exception with significant decreases in the amount of melanin and number of melanocytes in the epidermis. Thus, a novel in vivo technique that can assess the risk of leukoderma caused by 2% rhododenol was developed. The unique technique using tail skin has the potential to prevent chemical leukoderma in the future.

3.
Environ Health Prev Med ; 24(1): 36, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101002

RESUMO

BACKGROUND: Melanin is detectable in various sense organs including the skin in animals. It has been reported that melanin adsorbs toxic elements such as mercury, cadmium, and lead. In this study, we investigated the adsorption of molybdenum, which is widely recognized as a toxic element, by melanin. METHODS: Molybdenum level of the mouse skin was measured by inductively coupled plasma mass spectrometry. The pigmentation level of murine skin was digitalized as the L* value by using a reflectance spectrophotometer. An in vitro adsorption assay was performed to confirm the interaction between molybdenum and melanin. RESULTS: Our analysis of hairless mice with different levels of skin pigmentation showed that the level of molybdenum increased with an increase in the level of skin pigmentation (L* value). Moreover, our analysis by Spearman's correlation coefficient test showed a strong correlation (r = - 0.9441, p < 0.0001) between L* value and molybdenum level. Our cell-free experiment using the Langmuir isotherm provided evidence for the adsorption of molybdenum by melanin. The maximum adsorption capacity of 1 mg of synthetic melanin for molybdenum was 131 µg in theory. CONCLUSION: Our in vivo and in vitro results showed a new aspect of melanin as an adsorbent of molybdenum.


Assuntos
Melaninas/química , Molibdênio/química , Poluentes Químicos da Água/química , Adsorção , Animais , Melaninas/metabolismo , Camundongos , Camundongos Pelados , Camundongos Transgênicos , Molibdênio/metabolismo , Molibdênio/farmacologia , Pele/química , Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos dos fármacos , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/farmacologia
4.
Sci Rep ; 8(1): 16894, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30442994

RESUMO

About 80% of young people use personal listening devices (PLDs) including MP3 players to listen to music, which consists of sound components with various frequencies. Previous studies showed that exposure to noise of high intensities affected balance in humans. However, there is no information about a frequency-dependent effect of sound components in music from a PLD on balance in young people. In this study, we determined the associations between sound component levels (dB) at 100, 1000 and 4000 Hz in music from a portable listening device (PLD) and balance objectively determined by posturography in young adults (n = 110). We divided the subjects into two groups (low and high exposure groups) based on cut-off values of sound component levels at each frequency using receiver operating characteristic (ROC) curves. Balance in the high exposure group (≥46.6 dB) at 100 Hz was significantly better than that in low exposure group in logistic regression models adjusted for sex, BMI, smoking status and alcohol intake, while there were no significant associations at 1000 and 4000 Hz. Thus, this study demonstrated for the first time that the sound component at 100 Hz with more than 46.6 dB in music improved balance in young adults.

5.
Artigo em Inglês | MEDLINE | ID: mdl-30366865

RESUMO

The hypercoagulable state in patients with cancer has been shown to be closely associated with ischemic stroke. However, it is unlikely that benign tumors are related to stroke. The development of benign uterine tumors is common in middle-aged women. Previous studies have shown cases of ischemic stroke with benign uterine tumor, but the causal relationship between these 2 remain unknown. We report a case of recurrent ischemic stroke in a middle-aged woman who had a benign uterine tumor. After excision, there was no recurrence for 2 years. Microemboli detection, clinical course and histological findings support a relationship between uterine tumor and ischemic stroke.

6.
Chemosphere ; 210: 384-391, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30015129

RESUMO

At present, beneficial effects of melanin and harmful effects of barium have been reported. However, little is known about the adsorption of barium, and even less is known about the biological significance of adsorption of barium by melanin. In this study, we showed that there was a strong correlation between the digitalized level of skin pigmentation and barium level in murine skin compared to the correlations between skin pigmentation level and levels of homologous elements of barium (magnesium, calcium and strontium). The concentration of subcutaneously injected barium in skin with a high level of pigmentation was higher than that in skin with a low level of pigmentation. Our cell-free experiment using the Langmuir isotherm for adsorption of barium in synthetic melanin also provided direct evidence of adsorption of barium by melanin. We then investigated the biological significance of melanin-mediated barium adsorption. We found barium-mediated increase in transforming activity in pigmented melanocytes (melan-a) but not in unpigmented melanocytes (melan-c) after confirming that the barium level in melan-a melanocytes was 3.4-fold higher than that in melan-c melanocytes after culture of 5 µM barium for 24 h. Taken together, our results not only indicate adsorption of barium by melanin in mice, cells and cell-free systems but also suggest a disadvantageous effect of adsorption of barium by melanin on transforming activity in cultured cells.


Assuntos
Bário/metabolismo , Melaninas/metabolismo , Pigmentação/efeitos dos fármacos , Adsorção , Animais , Bário/farmacologia , Sistema Livre de Células , Células Cultivadas , Humanos , Melanócitos/metabolismo , Camundongos
7.
Anticancer Res ; 38(7): 4327-4331, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29970569

RESUMO

BACKGROUND/AIM: Malignant ascites contain many tumour-infiltrating lymphocytes. γδ T cells with antitumour activity have attracted attention as effector cells in cancer immunotherapy. Vδ2+ T cells were cultured from peripheral blood mononuclear cells (PBMCs) and ascites-infiltrating lymphocytes (AILs) to compare the differences in response to 2-methyl-3-butenyl-1-pyrophosphate (2M3B1-PP) and zoledronate (Zol) as antigens in vitro. MATERIALS AND METHODS: To expand Vδ2+ T cells from PBMCs and AILs from 29 patients with cancer, these cells were cultured and subjected to analysis. RESULTS: The proliferation rate of Vδ2+ T cells was higher in both PBMCs and AILs when cultured with Zol than with 2M3B1-PP. Although Vδ2+ T cells show a higher rate of expansion in AILs compared to PBMCs, the number of mixed tumour cells in ascites was decreased when cultured with Zol. CONCLUSION: Vδ2+ T cells in AILs are cytotoxic to tumour cells in ascites and may be considered in adoptive immunotherapy.


Assuntos
Imunoterapia Adotiva/métodos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/imunologia , Líquido Ascítico/imunologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias/imunologia , Receptores de Antígenos de Linfócitos T gama-delta
8.
Taiwan J Obstet Gynecol ; 57(1): 115-118, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29458879

RESUMO

OBJECTIVE: Atypical polypoid adenomyoma (APAM) is an epithelial-mesenchymal mixed tumor which often develops in the uterine cavity of reproductive age women, requiring preservation of the reproductive functions. Preoperative endometrial biopsy may not yield histological diagnosis as the tumor is a solid smooth muscle tumor. The standard treatment option is a hysteroscopic resection for the diagnosis and the treatment at the same time. CASE REPORT: We report a case of rapidly-growing APAM successfully diagnosed preoperatively via transcervical punch biopsy followed by a laparoscopic resection. The mass was relatively large, had been located in the lower segment of the uterus, and the area of contact with the muscular layers was large. It was a complete removal and no recurrence had been observed 9 months after the operation. CONCLUSION: This is the first report of APAM treated by laparoscopic resection. The method may be a useful alternative when hysteroscopic surgery is inappropriate.


Assuntos
Adenomioma/patologia , Laparoscopia/métodos , Pólipos/patologia , Neoplasias Uterinas/patologia , Adenomioma/cirurgia , Adulto , Diagnóstico Diferencial , Endométrio/patologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Pólipos/cirurgia , Ultrassonografia/métodos , Neoplasias Uterinas/cirurgia
9.
RNA ; 24(4): 468-479, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29295890

RESUMO

Intracellular iron is tightly regulated by coordinated expression of iron transport and storage genes, such as transferrin receptor-1 (TfR1) and ferritin. They are primarily regulated by iron through iron-induced dissociation of iron-regulatory proteins (IRPs) from iron-responsive elements (IREs) in the 3'-UTR (untranslated region) of TfR1 or 5'-UTR of ferritin mRNA, resulting in destabilization of TfR1 mRNA and release of ferritin translation block. Thus high iron decreases iron transport via TfR1 mRNA degradation and increases iron storage via ferritin translational up-regulation. However, the molecular mechanism of TfR1 mRNA destabilization in response to iron remains elusive. Here, we demonstrate that miR-7-5p and miR-141-3p target 3'-TfR1 IREs and down-regulate TfR1 mRNA and protein expression. Conversely, miR-7-5p and miR-141-3p antagomiRs partially but significantly blocked iron- or IRP knockdown-induced down-regulation of TfR1 mRNA, suggesting the interplay between these microRNAs and IRPs along with involvement of another uncharacterized mechanism in TfR1 mRNA degradation. Luciferase reporter assays using 3'-UTR TfR1 IRE mutants suggested that the IREs C and E are targets of miR-7-5p and miR-141-3p, respectively. Furthermore, miR-7 expression was inversely correlated with TfR1 mRNA in human pancreatic adenocarcinoma patient samples. These results suggest a role of microRNAs in the TfR1 regulation in the IRP-IRE system.


Assuntos
Antígenos CD/genética , Proteínas Reguladoras do Ferro/genética , MicroRNAs/genética , RNA Mensageiro/biossíntese , Receptores da Transferrina/genética , Células 3T3 , Animais , Antígenos CD/biossíntese , Proliferação de Células/genética , Ferritinas/genética , Humanos , Ferro/metabolismo , Camundongos , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Receptores da Transferrina/biossíntese
10.
Anticancer Res ; 37(7): 3975-3979, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28668903

RESUMO

BACKGROUND: Frasier syndrome (FS) is characterized by gonadal dysgenesis and progressive nephropathy caused by mutation in the Wilm's tumor gene (WT1). We report a case of FS in which diagnosis was based on amenorrhea with nephropathy, and laparoscopically-removed streak gonad which revealed gonadoblastoma. CASE REPORT: At the age of 3 years, the patient developed nephrotic syndrome. This later became steroid-resistant and, by the age of 16 years, had progressed to end-stage renal failure with peritoneal dialysis. At the age of 17 years, the patient presented primary amenorrhea and was referred to our department. Physical examination was consistent with Tanner 1 development and external genitalia were female phenotype. Speculum examination showed uterine cervix and uterine body and bilateral ovaries were not palpable on pelvic examination. Multi-sliced computed tomography of abdomen and pelvis revealed streaked structure along the bilateral external iliac artery at pelvic wall and hypoplastic uterus. Serum testing revealed primary hypogonadism pattern, elevated follicle-stimulating hormone and luteinizing hormone with low concentrations of estradiol and testosterone. The patient underwent genetic counseling with her parents. Chromosomal status was 46XY karyotype and DNA sequencing confirmed FS due to a heterozygous WT1 mutation (IVS9+5G>A). Elective laparoscopic bilateral salpingo-oophorectomy was performed to avoid increased risk for gonadoblastoma. Pathological examination revealed gonadoblastoma in the right gonad. CONCLUSION: Although a rare disease, the diagnosis of FS should be considered in the case of primary amenorrhea with nephropathy. Prophylatic gonadectomy is recommended due to the high risk of gonadoblastoma in the dysgenetic gonad.


Assuntos
Síndrome de Frasier/cirurgia , Gonadoblastoma/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Proteínas WT1/genética , Adolescente , Feminino , Síndrome de Frasier/complicações , Síndrome de Frasier/genética , Disgenesia Gonadal 46 XY , Humanos , Mutação , Ovariectomia , Salpingectomia , Tomografia Computadorizada por Raios X
12.
Prenat Diagn ; 37(8): 781-787, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28591488

RESUMO

OBJECTIVE: Maternal cell contamination (MCC) is known to increase the risk of misdiagnosis in prenatal diagnosis as well as in diagnostic tests for the products of conception (POC) from miscarriages. We aimed to develop a data correction method to salvage fetal karyotype information from single-nucleotide polymorphism (SNP) array data for POC with MCC when parental genotype data are available. METHODS: We obtained SNP array data from mixed genomic DNAs of a mother-child pair and used the dataset to assess the accuracy of data correction. We subsequently applied our method to miscarriage specimens with MCC. RESULTS: We adopted a linear interpolation model as a data correction method and implemented the method in an R package, snpsal. We successfully determined the fetal karyotypes of two miscarriage specimens that were previously undiagnosed due to MCC to be normal in one case and trisomy 16 in the other case using snpsal. CONCLUSION: The R package, snpsal, developed in this study facilitates rapid and accurate estimation of the fetal karyotype from SNP array data for POC with MCC. © 2017 John Wiley & Sons, Ltd.


Assuntos
Feto/química , Cariotipagem/métodos , Aborto Espontâneo/patologia , Feminino , Feto/patologia , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Gravidez
13.
Cell Signal ; 33: 69-78, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28229933

RESUMO

Lamins are important constituents of the nuclear inner membrane and provide a platform for transcription factors and chromatin. Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS). Oxidative stress appears to be involved in the pathogenesis of HGPS, although the mechanistic role of progerin remains elusive. Here we examined whether nuclear lamins are important for a cellular antioxidant mechanism, and whether progerin compromises it. We investigated the activation of nuclear factor-E2-related factor 2 (Nrf2) which regulates various antioxidant genes including heme oxygenase-1 (HMOX1), following exposure to sodium arsenite or cadmium chloride in lamin knockdown human cell lines and primary HGPS human fibroblasts. Knocking down lamin A/C, or B, or all nuclear lamins simultaneously in three human cell lines (HaCaT, SW480, and K562) did not impair arsenite- or cadmium-induced activation of Nrf2. Progerin-expressing human primary HGPS fibroblasts showed lower basal levels of HMOX1 and NQO1 expression; however, in response to arsenic stress both normal and HGPS primary fibroblasts showed Nrf2 nuclear accumulation along with upregulation and phosphorylation of p62/SQSTM1 at Ser351, downregulation of Keap1, and comparable expression of an array of downstream Nrf2-regulated antioxidant genes. We also observed new forms of cleaved lamin A, B1 and B2 induced by cadmium stress although their roles in the Nrf2 antioxidant system need further investigation. These results suggest that the nuclear lamins and progerin have marginal roles in the activation of the antioxidant Nrf2 response to arsenic and cadmium.


Assuntos
Antioxidantes/metabolismo , Arsênico/toxicidade , Cádmio/toxicidade , Núcleo Celular/metabolismo , Lamina Tipo A/metabolismo , Laminas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular Tumoral , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Heme Oxigenase-1/metabolismo , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Fosforilação/efeitos dos fármacos , Progéria/metabolismo , Progéria/patologia , Proteína Sequestossoma-1/metabolismo
14.
J Mol Biol ; 429(1): 64-78, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-27884605

RESUMO

Cyclic AMP-response element-binding protein (CREB) plays key transcriptional roles in cell metabolism, proliferation, and survival. Ser133 phosphorylation by protein kinase A (PKA) is a well-characterized CREB activation mechanism. Homeodomain-interacting protein kinase (HIPK) 2, a nuclear serine/threonine kinase, activates CREB through Ser271 phosphorylation; however, the regulatory mechanism remains uncharacterized. Transfection of CREB in HEK293 cells together with the kinase demonstrated that HIPK2 phosphorylated CREB at Ser271 but not Ser133; likewise, PKA phosphorylated CREB at Ser133 but not Ser271, suggesting two distinct CREB regulatory mechanisms by HIPK2 and PKA. In vitro kinase assay revealed that HIPK2, and HIPK1 and HIPK3, directly phosphorylated CREB. Cells exposed to 10µM sodium arsenite increased the stability of HIPK1 and HIPK2 proteins, leading to CREB activation via Ser271 phosphorylation. Phospho-Ser271 CREB showed facilitated interaction with the TFIID subunit coactivator TAF4 assessed by immunoprecipitation. Furthermore, a focused gene array between cells transfected with CREB alone and CREB plus HIPK2 over empty vector-transfected control displayed 14- and 32-fold upregulation of cyclin A1, respectively, while no upregulation was displayed by HIPK2 alone. These results suggest that the HIPK2-phospho-Ser271 CREB axis is a new arsenic-responsive CREB activation mechanism in parallel with the PKA-phospho-Ser133 CREB axis.


Assuntos
Arsênico/metabolismo , Proteínas de Transporte/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Serina-Treonina Quinases/metabolismo , Ativação Transcricional , Linhagem Celular , Perfilação da Expressão Gênica , Humanos , Fosforilação , Serina/metabolismo
15.
Trends Mol Med ; 22(12): 1077-1090, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27825668

RESUMO

Iron is an essential nutrient for life. During infection, a fierce battle of iron acquisition occurs between the host and bacterial pathogens. Bacteria acquire iron by secreting siderophores, small ferric iron-binding molecules. In response, host immune cells secrete lipocalin 2 (also known as siderocalin), a siderophore-binding protein, to prevent bacterial reuptake of iron-loaded siderophores. To counter this threat, some bacteria can produce lipocalin 2-resistant siderophores. This review discusses the recently described molecular mechanisms of siderophore iron trafficking between host and bacteria, highlighting the therapeutic potential of exploiting pathogen siderophore machinery for the treatment of antibiotic-resistant bacterial infections. Because the latter reflect a persistent problem in hospital settings, siderophore-targeting or siderophore-based compounds represent a promising avenue to combat such infections.


Assuntos
Bactérias/metabolismo , Infecções Bacterianas/metabolismo , Interações Hospedeiro-Patógeno , Ferro/metabolismo , Lipocalina-2/metabolismo , Sideróforos/metabolismo , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/imunologia , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Descoberta de Drogas , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Ferro/imunologia , Lipocalina-2/imunologia , Sideróforos/imunologia
16.
Antioxid Redox Signal ; 25(17): 953-964, 2016 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-27245349

RESUMO

AIMS: Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is the master transcriptional regulator of antioxidant gene expression. On increased oxidative stress, an adaptor for Nrf2 degradation, Kelch-like ECH-associated protein 1 (Keap1), is directly modulated by oxidants in the cytoplasm, which results in stabilization and activation of Nrf2. Nrf2 is also constitutively active, to some extent, in the absence of exogenous oxidative stress. We have previously demonstrated that intestinal epithelium-specific TGF-ß-activated kinase 1 (TAK1) deletion downregulates the level of Nrf2 protein, resulting in an increase of reactive oxygen species (ROS) in a mouse model. We aim at determining the mechanism by which TAK1 modulates the level of Nrf2. RESULTS: We found that TAK1 upregulated serine 351 phosphorylation of an autophagic adaptor protein, p62/Sequestosome-1 (SQSTM1), which facilitates interaction between p62/SQSTM1 and Keap1 and subsequent Keap1 degradation. This, ultimately, causes increased Nrf2. Tak1 deficiency reduced the phosphorylation of p62/SQSTM1, resulting in decreased steady-state levels of Nrf2 along with increased Keap1. We also found that this regulation is independent of the canonical redox-mediated Nrf2 activation mechanism. In Tak1-deficient intestinal epithelium, a synthetic phenolic electrophile, butylated hydroxyanisole still effectively upregulated Nrf2 and reduced ROS. INNOVATION: Our results identify for the first time that TAK1 is a modulator of p62/SQSTM1-dependent Keap1 degradation and maintains the steady state-level of Nrf2. CONCLUSION: TAK1 regulates Nrf2 through modulation of Keap-p62/SQSTM1 interaction. This regulation is important for homeostatic antioxidant protection in the intestinal epithelium. Antioxid. Redox Signal. 25, 953-964.


Assuntos
Antioxidantes/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína Sequestossoma-1/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Mucosa Intestinal/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , MAP Quinase Quinase Quinases/genética , Camundongos , Camundongos Knockout , Modelos Biológicos , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Ligação Proteica , Proteólise , Espécies Reativas de Oxigênio/metabolismo
17.
Anticancer Res ; 36(7): 3579-84, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27354626

RESUMO

AIM: To evaluate the response of mesothelial cells and macrophages in the peritoneal fluid of epithelial ovarian malignant tumors using flow cytometry immunophenotyping. MATERIALS AND METHODS: Thirteen peritoneal fluid samples collected from surgery or scentesis of epithelial ovarian malignant tumor patients were assayed using flow cytometry. Cytological and pathological diagnosis was performed on the same ascites and resected tumor specimens. Samples were treated with antibodies against established markers of mesothelial cells (podoplanin), macrophages (CD14) and the hyaluronan receptor (CD44). RESULTS: A significant association was observed between the results of cytology and expression of podoplanin, CD44 and CD14 (p<0.05) in peritoneal macrophages. No significant association was observed between the results of cytology and expression of podoplanin, CD44 and CD14 in mesothelial cells in ascites. CONCLUSION: Expression of surface molecules, such as podoplanin, CD44 and CD14 was increased in the peritoneal macrophages of epithelial ovarian cancer patients, suggesting that the cell-cell or cell-matrix interaction was enhanced during cancer dissemination in the peritoneum. Analysis of the peritoneal fluid using flow cytometry immunophenotyping may be useful for evaluating the diagnosis and pathophysiology of ovarian cancer dissemination.


Assuntos
Adenocarcinoma/secundário , Macrófagos Peritoneais/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Adulto , Idoso , Ascite/patologia , Células Epiteliais/patologia , Feminino , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade
18.
Trends Biochem Sci ; 41(3): 274-286, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26725301

RESUMO

Iron is necessary for life, but can also cause cell death. Accordingly, cells evolved a robust, tightly regulated suite of genes for maintaining iron homeostasis. Previous mechanistic studies on iron homeostasis have granted insight into the role of iron in human health and disease. We highlight new regulators of iron metabolism, including iron-trafficking proteins [solute carrier family 39, SLC39, also known as ZRT/IRT-like protein, ZIP; and poly-(rC)-binding protein, PCBP] and a cargo receptor (NCOA4) that is crucial for release of ferritin-bound iron. We also discuss emerging roles of iron in apoptosis and a novel iron-dependent cell death pathway termed 'ferroptosis', the dysregulation of iron metabolism in human pathologies, and the use of iron chelators in cancer therapy.


Assuntos
Morte Celular , Homeostase , Ferro/metabolismo , Humanos
19.
Gynecol Oncol ; 139(3): 429-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26456138

RESUMO

OBJECTIVE: To determine the primary remission rates and predictors of drug resistance in patients with post-molar low-risk gestational trophoblastic neoplasia (GTN) who were treated with a 5-day intramuscular methotrexate (5-day IM MTX) or a 5-day drip infusion etoposide (5-day DIV ETP) regimen. METHODS: Between 1980 and 2014, 166 consecutive patients with low-risk post-molar GTN were initially treated with a 5-day IM MTX or a 5-day DIV ETP regimen. The primary remission rates, changes in chemotherapy due to drug resistance or toxicity, and relapse rates were compared. Furthermore, we analyzed the factors that influenced the development of resistance to MTX. RESULTS: Primary remission rates were significantly higher among the ETP-treated patients than among the MTX-treated patients. Among the 42 patients who required a change in chemotherapy, 23 patients (22.6%) and 4 patients (6.3%) were diagnosed as being resistant to MTX and EPT, respectively. Maternal age and the presence of metastasis did not significantly influence the development of MTX resistance, although higher FIGO scores and pre-treatment human chorionic gonadotropin (hCG) levels of >5×10(4)mIU/mL were significantly more common among patients who developed MTX resistance. Moreover, a <30% decrease in hCG after the first cycles of MTX chemotherapy was significantly associated with the development of MTX resistance. CONCLUSIONS: All patients with low-risk GTN eventually achieved complete remission, although several patients developed drug resistance to the first-line chemotherapy. A <30% decrease in hCG during the first chemotherapy cycle may be an early indicator of drug resistance after commencing a 5-day MTX regimen.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Mola Hidatiforme/tratamento farmacológico , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adulto , Antimetabólitos Antineoplásicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Gonadotropina Coriônica/sangue , Esquema de Medicação , Substituição de Medicamentos , Etoposídeo/efeitos adversos , Feminino , Humanos , Mola Hidatiforme/sangue , Mola Hidatiforme/secundário , Metotrexato/efeitos adversos , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uterinas/sangue , Neoplasias Uterinas/patologia , Adulto Jovem
20.
Kyobu Geka ; 68(5): 371-4, 2015 May.
Artigo em Japonês | MEDLINE | ID: mdl-25963786

RESUMO

A 74-year-old female patient experienced sudden and severe pain in her lower back and both legs. Upon examination, her femoral pulses were weak, and her legs were pale. Computed tomography revealed a 66-mm thoracic aneurysm in the distal arch and type B aortic dissection. Stenosis was present from the terminal aorta to the iliac arteries. The left common iliac artery was occluded at its bifurcation, and both lower limbs were ischemic. We performed bilateral axillary-femoral artery bypass, which improved blood flow to both limbs. The next day, it was apparent that compartment syndrome had developed in the patient's left leg. Rehabilitation therapy was effective for the compartment syndrome, the patient's symptoms resolved, and she was discharged. We later performed two-stage total arch replacement, and the subsequent clinical course has been without incident.


Assuntos
Aneurisma Dissecante/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Isquemia/etiologia , Perna (Membro)/irrigação sanguínea , Idoso , Aneurisma Dissecante/complicações , Aneurisma da Aorta Torácica/complicações , Feminino , Humanos , Imagem Tridimensional , Tomografia Computadorizada por Raios X
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