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2.
Toxicol Lett ; 318: 99-103, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31669098

RESUMEN

Fluorination preventing metabolic hydroxylation of 17ß-estradiol (E2) was applied to investigate the mechanisms underlying estrogen-induced carcinogenesis. Either 2-fluoro-17ß-estradiol (2-FE2) or 4-fluoro-17ß-estradiol (4-FE2) was administered subcutaneously for 52 weeks to August Copenhagen Irish (ACI) rats, the preferred animal model for human breast cancer. 4-FE2 induced frequent mammary tumors whereas 2-FE2 did not. The cumulative incidence of mammary tumors in rats treated with 4-FE2 was comparable to that observed with E2. The carcinogenic results were supported by histological examination of mammary glands of fluorinated estrogen-treated ACI rats. To evaluate the estrogenic potential of the fluorinated estrogens, 2-FE2 or 4-FE2 was administrated subcutaneously to ovariectomized rats. Both 4-FE2 and 2-FE2 showed high uterotrophic potency. Our results indicate that estrogenic potential may not be the sole factor driving mammary tumorigenesis. Since fluorination inhibits metabolic hydroxylation of E2 at the substituted position, the carcinogenic effect may occur through the metabolic activation of 2-hydroxylated E2, in combination with the compound's estrogenic potency.


Asunto(s)
Neoplasias de la Mama/inducido químicamente , Transformación Celular Neoplásica/inducido químicamente , Estradiol/análogos & derivados , Animales , Neoplasias de la Mama/patología , Transformación Celular Neoplásica/patología , Estradiol/toxicidad , Femenino , Tamaño de los Órganos/efectos de los fármacos , Ratas Endogámicas ACI , Medición de Riesgo , Útero/efectos de los fármacos , Útero/patología
3.
Medicine (Baltimore) ; 98(50): e18349, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31852135

RESUMEN

BACKGROUND: Particulate matter (PM) acts as an environment pollutant and thus plays a vital role in the development of human lung cancer. Whether PM is a risk factor for breast cancer (BC) morbidity and mortality, however, is not clear. Recently, several studies have reported inconsistent results for the association between PM and BC risk. This meta-analysis examines the indefinite relationship between exposure to PM and BC morbidity and mortality. METHODS: Based on a search of Pubmed, Embase, Web of Science and Cochrane Library, the hazard ratio (HR) and 95% confidence interval (CI) were extracted and analyzed by Review Manager 5.3 and Stata14.0 to estimate the association between PM and BC morbidity and mortality. The heterogeneity for the included studies was evaluated using a Chi-square test and the I statistic. Forest plot was used to illustrate the pooled HR and mean difference. A Funnel plot, Begg test, and Egger test were performed to explore the publication bias between the included studies.All analyses were based on previous published studies, thus, no ethical approval and patient consent are required. RESULTS: A total of 14 of 284 publications with 1,004,128 BC cases were gathered. The analysis showed each 10 µg/m of PM2.5 (diameter ≤2.5 µm) was associated with 1.17 (95% CI: 1.05-1.30, P = .004) fold risk BC mortality, and each 10 µg/m of PM10 (diameter ≤10 µm) was associated with 1.11 (95% CI: 1.02-1.21, P = .021) fold risk BC mortality. However, neither PM10 nor PM2.5 was found to be significantly associated with BC morbidity. Publication bias was detected in studies on PM2.5 and BC mortality. CONCLUSIONS: Our study suggests that PM exposure may raise the mortality but not the morbidity of BC. Still, further studies may be necessary to confirm this finding.


Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Neoplasias de la Mama/mortalidad , Exposición a Riesgos Ambientales/efectos adversos , Material Particulado/análisis , Adulto , Anciano , Neoplasias de la Mama/inducido químicamente , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo
4.
J Environ Pathol Toxicol Oncol ; 38(2): 153-163, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31679278

RESUMEN

Chemobrain is a significant post-chemotherapy complication for which no approved treatments are available. We had previously identified that rutin inhibits doxorubicin (Dox-) -induced cognitive decline in healthy rats. However, it was important to also establish that it does so in rats with mammary carcinoma without compromising Dox's antitumor potential. Mammary carcinoma was induced in female rats by intraperitonial administration of N-methyl-N-nitrosourea (i.p.). Rats that developed mammary carcinoma were treated with Dox after pretreatment with vehicle or rutin. After Dox exposure (50 days), episodic and spatial memory was assessed using the novel object recognition task and the Morris water maze, respectively. Tumor progression was evaluated by measurement of tumor weight and volume and histological analysis. Blood samples were collected to estimate hematological parameters. Oxidative status and TNF-α levels were estimated in brain homogenates. Dox treatment significantly reduced tumor size and volume. Pretreatment with rutin did not significantly alter Dox's tumor suppression potential, suggesting that it does not influence Dox's anticancer activity. In addition, rutin ameliorated Dox-induced cognitive decline, myelosuppression, and brain oxidative stress. The present study indicates that rutin protects against Dox-induced cognitive decline and myelosuppression without affecting its antitumor potential.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/inducido químicamente , Doxorrubicina/farmacología , Metilnitrosourea/toxicidad , Sustancias Protectoras/farmacología , Rutina/farmacología , Animales , Disfunción Cognitiva/inducido químicamente , Doxorrubicina/toxicidad , Femenino , Ratas , Ratas Sprague-Dawley
5.
Presse Med ; 48(11 Pt 1): 1295-1300, 2019 Nov.
Artículo en Francés | MEDLINE | ID: mdl-31735524

RESUMEN

Can menopausal hormone therapy (HT) be used in hypertensive women? The group of experts of the French Society of Hypertension has carried out a review of the recent literature in order to answer this question, based on the most recent scientific publications. If use of oral HT is associated with a discreet increase in blood pressure, the transdermal route seems to be safer. The first results of major randomized trials of HT had alerted to an increase in cardiovascular events and breast cancer with the use of oral HT, generally, tipping the benefit-risk balance of the deleterious side. Complementary analyzes have shown the importance of the window of intervention (less than 10 years after the menopause) and the age of the woman to start the HT. On the contrary, they have shown a significant decrease of the coronary events. For woman suffering from hypertension and important climacteric symptoms, it is important to evaluate the whole cardiovascular risk in order to decide the possibility of prescribing a HT. Thus, the group of experts proposes a prescription assistance algorithm based on the stratification of cardiovascular risk, always favoring, when it is authorized, HT by transdermal route of administration.


Asunto(s)
Neoplasias de la Mama/inducido químicamente , Enfermedades Cardiovasculares/inducido químicamente , Terapia de Reemplazo de Estrógeno/métodos , Hipertensión , Menopausia , Administración Cutánea , Administración Oral , Factores de Edad , Algoritmos , Presión Sanguínea/efectos de los fármacos , Contraindicaciones de los Medicamentos , Terapia de Reemplazo de Estrógeno/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
6.
Presse Med ; 48(11 Pt 1): 1261-1264, 2019 Nov.
Artículo en Francés | MEDLINE | ID: mdl-31735525

RESUMEN

The impact of antihypertensive drugs on blood pressure does not differ according to the sex. There are women-specific conditions or medical conditions encountered more frequently among womens that guide the selection of therapy such as a desire to become pregnant, a pregnancy, a polycystic ovarian syndrome, breast cancer, osteoporosis or migraine.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Factores de Edad , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Neoplasias de la Mama/inducido químicamente , Femenino , Humanos , Trastornos Migrañosos , Osteoporosis/complicaciones , Osteoporosis/tratamiento farmacológico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Embarazo , Factores Sexuales , Espironolactona/efectos adversos
7.
Chem Commun (Camb) ; 55(95): 14287-14290, 2019 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-31712798

RESUMEN

A novel bright near-infrared II (NIR-II, 1000-1700 nm) fluorescent probe with excellent water-solubility, superior photostability, and excellent in vitro and in vivo biocompatibility was facilely synthesized for in vivo biomedical imaging of xenograft breast tumor and chemically induced spontaneous breast carcinoma. To the best of our knowledge, it is the first time that the superior practical applications of this NIR-II probe in dimethylbenzanthracene (DMBA)-induced rat mammary carcinoma imaging and image-guided rat carcinoma surgery were demonstrated.


Asunto(s)
Materiales Biocompatibles/química , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Colorantes Fluorescentes/química , 9,10-Dimetil-1,2-benzantraceno , Animales , Neoplasias de la Mama/inducido químicamente , Femenino , Humanos , Rayos Infrarrojos , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/diagnóstico por imagen , Neoplasias Mamarias Experimentales/cirugía , Ratones , Ratones Endogámicos , Ratas , Ratas Sprague-Dawley
9.
Cas Lek Cesk ; 158(3-4): 107-111, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31416316

RESUMEN

Tibolon is the only therapeutic approach to climacteric symptoms, prevention of osteoporosis and urogenital atrophy with the same efficacy as hormone replacement therapy. Tibolon has more positive effects on sexuality and mood changes in menopausal women. It decreases the mammographic density. Its safety for breast cancer is the same as for only estrogen therapy and better than for estrogen-gestagen therapy. Tibolon is the first choice for postmenopausal women with mood and sexuality disorders, women with mastodynia and high mammographic density.


Asunto(s)
Moduladores de los Receptores de Estrógeno , Norpregnenos , Osteoporosis , Neoplasias de la Mama/inducido químicamente , Clima , Moduladores de los Receptores de Estrógeno/efectos adversos , Moduladores de los Receptores de Estrógeno/uso terapéutico , Estrógenos , Femenino , Humanos , Menopausia , Norpregnenos/efectos adversos , Norpregnenos/uso terapéutico , Osteoporosis/prevención & control , Progestinas
10.
Arch Environ Contam Toxicol ; 77(4): 480-489, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31324944

RESUMEN

Breast cancer is a multifactorial disease and its etiology is linked to multiple risk factors. There are shreds of controversial evidence that exposure to organochlorine pesticides (OCPs) are important in the etiology of breast cancer. The present study aimed to determine the circulating levels of OCPs in patients with breast tumors in Southeastern of Iran. This case-control study included 27 patients with malignant breast tumors (MBT), 31 patients with benign breast tumors (BBT), and 27 healthy women as a control group. Serum OCPs levels, including α-hexachlorocyclohexane (α-HCH), ß-HCH, γ-HCH, 2,4-dichlorodiphenyltrichloroethane (2,4-DDT), 4,4-DDT, 2,4-dichlorodiphenyldichloroethylene (2,4-DDE), and 4,4-DDE, were measured using gas chromatography. Our data revealed significantly higher concentrations of 2,4-DDT in MBT and BBT groups compared with control ones (P < 0.001 for both comparisons). Patients with breast cancer suffered significantly higher accumulation levels of 4,4-DDE compared with control subjects (P = 0.04). Significant correlations were found among organochlorine compounds with each other in both patients' groups. There was a significant positive correlation between body mass index and serum levels of 2,4-DDT in BBT group (r = 0.407, P = 0.02). The present findings suggest that the serum levels of 4,4-DDE and 2,4-DDT are associated with an increase in the risk of breast cancer in Southeastern women of Iran.


Asunto(s)
Neoplasias de la Mama/sangre , Neoplasias de la Mama/inducido químicamente , Hidrocarburos Clorados/sangre , Plaguicidas/sangre , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Cromatografía de Gases , DDT/sangre , DDT/toxicidad , Diclorodifenil Dicloroetileno/sangre , Diclorodifenil Dicloroetileno/toxicidad , Femenino , Hexaclorociclohexano/sangre , Hexaclorociclohexano/toxicidad , Humanos , Hidrocarburos Clorados/toxicidad , Irán , Persona de Mediana Edad , Plaguicidas/toxicidad , Factores de Riesgo
11.
Transplant Proc ; 51(6): 1848-1852, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31256869

RESUMEN

The incidence rate of breast fibroadenomas is higher among female kidney transplant (KT) patients treated using cyclosporine (CsA) for immunosuppression than in the general population. As such, there is an effort to convert immunosuppression from CsA or tacrolimus to sirolimus. Our aim was to assess the reversibility of a breast fibroadenoma after conversion in a small cohort of female KT recipients. This was an open-label, single-arm study including 128 female KT recipients, with a positive finding of a breast fibroadenoma in 15. Lesions were classified according to the Breast Imaging Reporting and Data System (BIRADS). Among these 15, a total of 7 converted from tacrolimus to sirolimus and 8 converted from CsA. We measured the change in BIRADS category and hormone and cytokine levels from baseline to 12 months after conversion. The primary outcome was progression or reversal of existing fibroadenomas at 12 months after conversion. Secondary outcomes were differences in hormone and cytokine levels. Conversion from CsA or tacrolimus to sirolimus had no significant effect on the BIRADS classification. However, conversion to sirolimus did produce a significant decrease in the level of transforming growth factor ß cytokine, this level being closely associated with fibroadenomas. Conversion from a calcineurin inhibitor to sirolimus can block the progression of fibroadenomas. Further research is needed to confirm our results.


Asunto(s)
Neoplasias de la Mama/inducido químicamente , Inhibidores de la Calcineurina/efectos adversos , Fibroadenoma/inducido químicamente , Inmunosupresores/administración & dosificación , Complicaciones Posoperatorias/inducido químicamente , Sirolimus/administración & dosificación , Adulto , Neoplasias de la Mama/epidemiología , Ciclosporina/efectos adversos , Sustitución de Medicamentos/métodos , Femenino , Fibroadenoma/epidemiología , Rechazo de Injerto , Humanos , Inmunosupresión/efectos adversos , Inmunosupresión/métodos , Inmunosupresores/efectos adversos , Incidencia , Trasplante de Riñón/efectos adversos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Tacrolimus/efectos adversos
12.
Cancer Sci ; 110(10): 3089-3097, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31325197

RESUMEN

Delphinidin, one of the main anthocyanidins, has potent anti-cancer properties. In this study, we investigated the effect of delphinidin on 1-methyl-1-nitrosourea (MNU)-induced breast carcinogenesis on rats and the mechanism of delphinidin via negative regulation of the HOTAIR/microRNA-34a axis. We found administration of delphinidin could effectively suppress MNU-induced mammal breast carcinogenesis. Delphinidin downregulated the level of HOTAIR and upregulated miR-34a in breast carcinogenesis. Western blot analysis confirmed that delphinidin treatment can significantly decrease the expression of ß-catenin, glycogen synthase kinase-3ß (Gsk3ß), c-Myc, cyclin-D1, and matrix metalloproteinase-7(MMP-7) expression in breast cancer cells, and inhibition of miR-34a significantly reduced the effect of delphinidin on c-Myc, cyclin-D1, and MMP-7. HOTAIR overexpression also blocked the effect of delphinidin on miR-34a and the Wnt/ß-catenin signaling pathway in MDA-MB-231 cells. RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay results showed that delphinidin upregulated miR-34a by inhibiting HOTAIR, coupled with enhancement of the zeste homolog 2 (EZH2) and histone H3 Lys27 trimethylation (H3K27me3). This study indicated that delphinidin may potentially suppress breast carcinogenesis and exert its anti-cancer effect through the HOTAIR/miR-34a axis. These findings provided new evidence for the use of delphinidin in preventing breast carcinogenesis.


Asunto(s)
Antocianinas/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Metilnitrosourea/toxicidad , MicroARNs/genética , ARN Largo no Codificante/genética , Animales , Antocianinas/farmacología , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Histonas/metabolismo , Humanos , Ratas , Vía de Señalización Wnt/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
13.
BMC Womens Health ; 19(1): 72, 2019 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-31159800

RESUMEN

BACKGROUND: Oral contraceptives (OCs) use has been linked to increased risk of breast cancer (BC) in several reports from the world. Limited number of similar studies have been conducted in the Middle Eastern female population. This study aimed to explore any possible correlation between the contemporary and duration of OCs use among Jordanian women and the risk of breast cancer. METHODS: A case control study was conducted in 450 Jordanian women (225 as cases and 225 as controls), aged 18 to 65. Chi-square test was used to study the association between risk of breast cancer and different factors. Mann Whitney-U test was employed to evaluate the relation between time-dependent risk factor and breast cancer. RESULTS: Our results indicated that regular use of OCs exhibited association with increased risk of breast cancer (OR = 2.25, 95% CI 1.34-2.79; p = 0.002), while the duration of OCs use was not associated with the increased risk of breast cancer (p > 0.05). In addition, other factors demonstrated significant association with the increased risk of breast cancer such as age at puberty, age at menopause, previous pregnancies, menopausal status, and family history of cancer. CONCLUSIONS: regular use of OCs may be associated with increased risk of breast cancer in Jordanian women. A larger sample size in multi-center setting study is required to confirm this finding among the Jordanian female population.


Asunto(s)
Neoplasias de la Mama/inducido químicamente , Anticoncepción/efectos adversos , Anticonceptivos Orales/efectos adversos , Adolescente , Adulto , Anciano , Neoplasias de la Mama/epidemiología , Estudios de Casos y Controles , Anticoncepción/métodos , Anticonceptivos Orales/administración & dosificación , Anticonceptivos Orales Combinados/efectos adversos , Congéneres del Estradiol/efectos adversos , Femenino , Humanos , Jordania , Persona de Mediana Edad , Factores de Riesgo , Maduración Sexual , Adulto Joven
14.
Int J Mol Sci ; 20(12)2019 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-31234310

RESUMEN

As the majority of experimental studies suggest cadmium being metalloestrogen, we examined cadmium/breast cancer (BC) association by histological and tumor receptor subtype in 509 invasive BC patients and 1170 controls. Urinary cadmium was determined by atomic absorption spectrometry, and categorized using tertiles of its distribution in the controls: <0.18, 0.18-0.33, >0.33 kg × 10-9/kg × 10-3 creatinine. Relative to the lowest category of urinary cadmium adjusted odds ratio (OR) of ductal BC was 1.18 (95% confidence interval (CI): 0.89-1.58) in the intermediate and 1.53 (95% CI: 1.15-2.04) in the highest category. There was a significant association for hormone receptor-positive ductal BC: ORs per category increase were 1.34 (95% CI: 1.14-1.59) for estrogen receptor-positive (ER+), 1.33 (95% CI: 1.09-1.61) for progesterone receptor-positive (PR+) and 1.35 (95% CI: 1.11-1.65) for ER+/PR+ BC. We found a significant association between cadmium and human epidermal growth factor receptor 2-negative (HER2-) ductal BC. The strongest association with cadmium was for ER+/PR+/HER2- ductal BC. The associations between cadmium and lobular BC with hormone receptor-positive and HER2- were positive but insignificant. There was no evidence that the associations with cadmium differed for cancers with different tumor histology (p-heterogeneity > 0.05). This study provides evidence that urinary cadmium is associated with the risk of hormone receptor-positive and HER2- breast cancer independent of tumor histology.


Asunto(s)
Neoplasias de la Mama/inducido químicamente , Cadmio/efectos adversos , Carcinoma Ductal de Mama/inducido químicamente , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/orina , Cadmio/orina , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama/orina , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Receptor ErbB-2/análisis , Receptores Estrogénicos/análisis , Receptores de Progesterona/análisis , Factores de Riesgo
15.
Methods Mol Biol ; 1966: 203-210, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31041749

RESUMEN

The chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) has been used for many decades to induce skin, mammary, and ovarian tumors in mice. There are however a wide range of doses and treatment regimens in the literature that sometimes confound comparative interpretations of different studies. Here we describe a proven method to generate in vivo DMBA-mediated murine mammary tumors to enable consistent studies of the cell targeted role of genes of interest during this process.


Asunto(s)
9,10-Dimetil-1,2-benzantraceno/toxicidad , Neoplasias de la Mama/metabolismo , Pruebas de Carcinogenicidad/métodos , Neoplasias Mamarias Experimentales/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Animales , Neoplasias de la Mama/inducido químicamente , Carcinógenos/toxicidad , Femenino , Neoplasias Mamarias Experimentales/inducido químicamente , Ratones
16.
Zhonghua Zhong Liu Za Zhi ; 41(5): 346-350, 2019 May 23.
Artículo en Chino | MEDLINE | ID: mdl-31137167

RESUMEN

Objective: To explore the feasibility of 7, 12-dimethylbenz[a] anthracene (DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection. Methods: A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg/kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg/kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg/kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor (PR), cytokeratin5/6 (CK5/6) and human epidermal factor receptor-2 (HER-2) was detected by immunohistochemical staining. Results: In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0% (4/20) tumor formation rate. The success rate of mammary cancer modeling was 10.0% (2/20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0% (9/20) tumor formation rate. The success rate of mammary cancer modeling was 40.0% (8/20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate (P>0.05) between the two groups (all P>0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group (P<0.05), whereas the tumor formation time was markedly shorter than that in the gavage group (P<0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER-2 but positive expression of ER, PR and CK5/6 with varying degrees. Conclusion: Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.


Asunto(s)
9,10-Dimetil-1,2-benzantraceno/toxicidad , Neoplasias de la Mama/patología , Modelos Animales de Enfermedad , Neoplasias Mamarias Experimentales/inducido químicamente , 9,10-Dimetil-1,2-benzantraceno/administración & dosificación , Administración Oral , Animales , Neoplasias de la Mama/inducido químicamente , Carcinógenos/administración & dosificación , Carcinógenos/toxicidad , Femenino , Inyecciones , Distribución Aleatoria , Tupaiidae
17.
Crit Rev Oncol Hematol ; 137: 123-130, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31014508

RESUMEN

The possibility that the use of hormonal contraceptives may increase the risk of breast cancer has been raised since many years. In the past this hypothesis has been dismissed on the basis that available data were generally derived from "old" studies in which relatively high hormone doses had been used. The recent publication of two studies that analysed data from women receiving low-dose hormonal contraception and showed a statistically significant increase in breast cancer contradicts this reassuring belief. The topic however is not settled, since different results were obtained in other studies and since hormonal contraception (HC) also has unquestionable positive effects such as a decrease in ovarian and in endometrial cancer. The aim of the present paper is to provide evidence that may help gynaecologists and oncologists in discussing with their patients the use of HC. Even if cancer phobia is a strong reason for not using or limiting HC, patients must be informed that notwithstanding the slightly increased breast cancer risk, the overall cancer risk may still be lower than non-users. Proper counselling may help the woman choose the most suitable contraception in the different phases of her life and on the basis of other conditions that may increase cancer risk such as overweight, smoking or family history.


Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/prevención & control , Anticonceptivos Hormonales Orales/administración & dosificación , Anticonceptivos Orales/administración & dosificación , Consejo/métodos , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/psicología , Anticonceptivos Orales/efectos adversos , Anticonceptivos Hormonales Orales/efectos adversos , Femenino , Estilo de Vida Saludable , Humanos , Riesgo
18.
Nat Commun ; 10(1): 1522, 2019 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-30944316

RESUMEN

Recent studies have demonstrated that chromatin architecture is linked to the progression of cancers. However, the roles of 3D structure and its dynamics in hormone-dependent breast cancer and endocrine resistance are largely unknown. Here we report the dynamics of 3D chromatin structure across a time course of estradiol (E2) stimulation in human estrogen receptor α (ERα)-positive breast cancer cells. We identified subsets of temporally highly dynamic compartments predominantly associated with active open chromatin and found that these highly dynamic compartments showed higher alteration in tamoxifen-resistant breast cancer cells. Remarkably, these compartments are characterized by active chromatin states, and enhanced ERα binding but decreased transcription factor CCCTC-binding factor (CTCF) binding. We finally identified a set of ERα-bound promoter-enhancer looping genes enclosed within altered domains that are enriched with cancer invasion, aggressiveness or metabolism signaling pathways. This large-scale analysis expands our understanding of high-order temporal chromatin reorganization underlying hormone-dependent breast cancer.


Asunto(s)
Neoplasias de la Mama/metabolismo , Cromatina/metabolismo , Antineoplásicos Hormonales/farmacología , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Núcleo Celular/metabolismo , Cromatina/química , Resistencia a Antineoplásicos , Epigénesis Genética , Estradiol/farmacología , Receptor alfa de Estrógeno/biosíntesis , Receptor alfa de Estrógeno/genética , Femenino , Humanos , Células MCF-7 , Modelos Moleculares , Regiones Promotoras Genéticas , Unión Proteica , Transducción de Señal , Tamoxifeno/farmacología , Factores de Transcripción
19.
Environ Sci Pollut Res Int ; 26(15): 15209-15217, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30924043

RESUMEN

Breast cancer is a global public health problem where it is the second most prevalent cancer. Historical cancer treatment with graviola has been reported. This study aimed to investigate the protective effects of graviola on 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat breast cancer. Fifty female Wistar rats were allocated into four groups: control group (gastro-gavaged by sesame oil), DMBA-treated group (gastro-gavaged a single dose of DMBA [50 mg/kg body mass, diluted in 1 ml sesame oil]) at the age 57 days, DMBA+G37-treated group (gastro-gavaged a single dose of DMBA [50 mg/kg body mass, diluted in 1 ml sesame oil]) at the age of 57 days plus graviola (200 mg/kg body mass) two times weekly (p.o.) at the age of 37 days till the end of the experiment, and DMBA+G57-treated group (received a single dose of DMBA [50 mg/kg body mass, diluted in 1 ml sesame oil]) plus graviola (200 mg/kg body mass) two times weekly at the age of 57 days until the end of the experiment. After the 30-week experimental period, blood samples were collected. Then, animals were sacrificed to determine the apoptotic indices, antioxidant status, and mammary gland tumor marker (CA 15-3). The DMBA upregulated the expression of one of the main anti-apoptotic genes: B-cell lymphoma protein 2 (BCL2) and estrogen receptor alpha (ER-α) gene. Moreover, it significantly increased breast lipid peroxidation and serum CA 15-3 but decreased breast antioxidant enzymatic activities (glutathione peroxidase, glutathione S-transferase, catalase, and superoxide dismutase). Nevertheless, administration of DMBA and graviola especially DMBA+G37 induced apoptosis through at least 1.5-fold in gene expression levels of pro-apoptotic genes: BCL2-associated X protein (BAX), tumor suppressor gene (P53), and cysteinyl-aspartic acid-protease-3 (caspase-3). A critical role of P53 in the regulation of the BCL2 and BAX has been reported. These proteins can determine if the cell undergoes apoptosis or cancels the process. Once the BAX gene activates caspase-3, there is no irreversible way toward cell death. Also, graviola ameliorated the DMBA effects on antioxidant enzymatic activities and tumor marker CA 15-3. This study concludes that graviola ameliorated DMBA-induced breast cancer potentially through upregulating apoptotic genes, downregulating the ER-α gene, increasing antioxidants, and decreasing lipid peroxidation levels.


Asunto(s)
9,10-Dimetil-1,2-benzantraceno/toxicidad , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/inducido químicamente , Caspasa 3/metabolismo , Catalasa/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Receptores Estrogénicos/metabolismo , Superóxido Dismutasa/metabolismo , Proteína X Asociada a bcl-2/genética , 9,10-Dimetil-1,2-benzantraceno/química , 9,10-Dimetil-1,2-benzantraceno/metabolismo , Animales , Antioxidantes/química , Caspasa 3/química , Catalasa/química , Femenino , Glutatión Peroxidasa/química , Peroxidación de Lípido , Ratas , Ratas Wistar , Superóxido Dismutasa/química , Proteína X Asociada a bcl-2/química
20.
Breast Cancer Res Treat ; 175(3): 741-748, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30895533

RESUMEN

PURPOSE: To address the possible association between the use of metformin, other forms of antidiabetic medication (ADM) and statins with the incidence of breast cancer in women with type 2 diabetes (T2D). METHODS: Data were collected from a Finnish nationwide diabetes database (FinDM). The study cohort consisted of women diagnosed with T2D in 1996-2011 in Finland. In full-cohort analysis, Poisson regression was used to estimate hazard ratios (HRs) in relation to use of metformin, insulin, other forms of oral ADM and statins. In nested case-control analysis, up to 20 controls were matched for age and duration of diabetes to each case of breast cancer. Conditional logistic regression was used to estimate HRs in relation to medication use and cumulative use of different forms of ADM, and statins. RESULTS: 2300 women were diagnosed with breast cancer during follow-up. No difference in breast cancer incidence was observed between metformin users [HR 1.02, 95% confidence interval (CI) 0.93-1.11] or statin users (HR 0.97, 95% CI 0.89-1.05) compared with non-users. In nested case-control analysis the results were similar. Use of insulin (HR 1.18, 95% CI 1.03-1.36) was associated with a slightly increased incidence of breast cancer. CONCLUSIONS: No evidence of an association between the use of metformin or statins and the incidence of breast cancer in women with T2D was found. Among insulin users, a slightly higher incidence of breast cancer was observed.


Asunto(s)
Neoplasias de la Mama/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Metformina/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/inducido químicamente , Estudios de Casos y Controles , Bases de Datos Factuales , Femenino , Finlandia/epidemiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Hipoglucemiantes/efectos adversos , Incidencia , Insulina/efectos adversos , Metformina/efectos adversos , Persona de Mediana Edad , Análisis de Regresión
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