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1.
Tumour Biol ; 42(1): 1010428319901052, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31959092

RESUMO

Feline invasive mammary carcinomas are characterized by their high clinical aggressiveness, rare expression of hormone receptors, and pathological resemblance to human breast cancer, especially triple-negative breast cancer (negative to estrogen receptor, progesterone receptor, and epidermal growth factor receptor type 2). Recent gene expression studies of triple-negative breast cancers have highlighted their heterogeneity and the importance of immune responses in their biology and prognostic assessment. Indeed, regulatory T cells may play a crucial role in producing an immune-suppressed microenvironment, notably in triple-negative breast cancers. Feline invasive mammary carcinomas arise spontaneously in immune-competent animals, in which we hypothesized that the immune tumor microenvironment also plays a role. The aims of this study were to determine the quantity and prognostic value of forkhead box protein P3-positive peritumoral and intratumoral regulatory T cells in feline invasive mammary carcinomas, and to identify an immune-suppressed subgroup of triple-negative basal-like feline invasive mammary carcinomas. One hundred and eighty female cats with feline invasive mammary carcinomas, treated by surgery only, with 2-year follow-up post-mastectomy, were included in this study. Forkhead box protein P3, estrogen receptor, progesterone receptor, Ki-67, epidermal growth factor receptor type 2, and cytokeratin 14 expression were assessed by automated immunohistochemistry. Peritumoral regulatory T cells were over 300 times more abundant than intratumoral regulatory T cells in feline invasive mammary carcinomas. Peritumoral and intratumoral regulatory T cells were associated with shorter disease-free interval and overall survival in both triple-negative (ER-, PR-, HER2-, N = 123 out of 180) and luminal (ER+ and/or PR+, N = 57) feline invasive mammary carcinomas. In feline triple-negative basal-like (CK14+) mammary carcinomas, a regulatory T-cell-enriched subgroup was associated with significantly poorer disease-free interval, overall survival, and cancer-specific survival than regulatory T-cell-poor triple-negative basal-like feline invasive mammary carcinomas. High regulatory T-cell numbers had strong and negative prognostic value in feline invasive mammary carcinomas, especially in the triple-negative basal-like subgroup, which might contain a "basal-like immune-suppressed" subtype, as described in triple-negative breast cancer. Cats with feline invasive mammary carcinomas may thus be interesting spontaneous animal models to investigate new strategies of cancer immunotherapy in an immune-suppressed tumor microenvironment.


Assuntos
Neoplasias Mamárias Animais/patologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Gatos , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica/métodos , Imunossupressão/métodos , Neoplasias Mamárias Animais/metabolismo , Prognóstico , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Microambiente Tumoral/fisiologia
2.
Bratisl Lek Listy ; 121(1): 43-50, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31950839

RESUMO

AIM: Noscapine, a naturally occurring alkaloid obtained from opium poppy, is a microtubule-targeting agent. This study is aimed to investigate the effects of noscapine on human breast cancer cell lines by comparing them with those of tamoxifen and docetaxel. METHODS: MCF-7 and MDA MB-23 cell lines were used to observe the effects of docetaxel, tamoxifen, and noscapine on cell proliferation. For each drug, cell blocks were prepared from cultured cells treated with IC50 dose of each drug and these were examined histologically. The expressions of Ki-67, Bcl-2, BAX, and cyclin-D1 were assessed immunohistochemically. RESULTS: Although noscapine showed cytotoxic effects on both cell lines in a time and dose dependent manner, MDA-MB-231 cells were more susceptible to its effects. Noscapine inhibited MCF-7 and MDA-MB-231 cells proliferation in vitro with IC50 value of 29 µM and 69 µM, respectively, which was comparable with IC50 of tamoxifen (40 µM and 50 µM) and docetaxel (43 nM and 32 nM). Noscapine showed anti-proliferative effects by decreasing Ki-67, cyclin-D1 and apoptotic effects by increasing BAX/Bcl-2 ratio in both breast cancer cells. Its effect was comparable with tamoxifen and docetaxel. CONCLUSION: Noscapine may be a good chemotherapeutic agent for the treatment of breast cancer, especially in estrogen receptor­negative breast cancer (Tab. 2, Fig. 7, Ref. 40).


Assuntos
Antineoplásicos , Apoptose , Neoplasias da Mama , Noscapina , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Humanos , Células MCF-7 , Noscapina/farmacologia , Receptores Estrogênicos , Tamoxifeno
3.
Zhonghua Bing Li Xue Za Zhi ; 49(1): 57-61, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31914536

RESUMO

Objective: To investigate the expression and clinicopathological significance of high mobility group box protein B1 (HMGB1) protein in breast cancer. Methods: The expression of HMGB1 protein in 26 normal breast tissues and 417 invasive breast cancer tissues diagnosed at Dongyang People's Hospital, Zhejiang Province from 2016 to 2018 were detected by immunohistochemical EnVision method. The relationship between nuclear and cytoplasmic HMGB1 protein expression and clinicopathologic features of breast cancer patients were analyzed. Results: The nuclear and cytoplasmic expression of HMGB1 protein was 80.8% (337/417) and 16.8% (70/417) respectively in breast cancer, and was 46.2%(12/26) and 0(0/26) respectively in normal breast tissue. Both nuclear and cytoplasmic expression of HMGB1 protein in breast cancer were significantly higher than normal breast tissue (P<0.001, P=0.046, respectively). The nuclear expression of HMGB1 protein was also higher in high grade, estrogen receptor (ER) negative, progesterone receptor (PR) negative (P=0.006, P=0.004, P<0.001, respectively); whereas the cytoplasmic expression of HMGB1 protein was also higher in high grade, estrogen receptor (ER) negative, progesterone receptor (PR) negative (P<0.001 in all) breast cancers. Multivariate logistic regression model showed that nuclear HMGB1 expression correlated with histologic grade (OR=2.188, 95%CI=1.078-4.443, P=0.030), while cytoplasmic HMGB1 expression correlated with histologic grade (OR=3.031, 95%CI=1.600-5.742, P=0.001), ER (OR=0.129, 95%CI=0.034-0.494, P=0.003) and TNM staging (OR=3.820, 95%CI=1.042-14.001, P=0.043). Multivariate analysis of Cox proportional hazard model showed that nuclear HMGB1 expression was an independent risk factor for the overall survival of breast cancer patients (HR=0.366, 95%CI=0.138-0.972, P=0.044). Conclusion: Nuclear and cytoplasmic HMGB1 proteins are related to multiple poor prognostic factors in breast cancer, and may be a potential biomarker for breast cancer treatment.


Assuntos
Neoplasias da Mama , Proteína HMGB1/metabolismo , Biomarcadores Tumorais , Humanos , Prognóstico , Receptores Estrogênicos
4.
Anticancer Res ; 40(1): 281-286, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892577

RESUMO

BACKGROUND/AIM: Neoadjuvant chemotherapy (NAC) for breast cancer (BC) is the gold standard treatment for locally advanced tumors (LABC) that aims at achieving a complete pathological response (pCR). Studies have been conducted to evaluate and identify te concordance between radiological, histopathological and biological variables of BC and final response to therapy, verified by definitive histological examination after surgery. PATIENTS AND METHODS: Ninety-five BC patients were examined and subjected to NAC. Immunohistochemical markers including oestrogen-receptor (ER), progesterone-receptor (PR), Ki67 index, and human epidermal growth factor receptor 2 (HER2) score were examined before and after neoadjuvant treatment. RESULTS: Younger age and a significant decrease in ER expression were associated with better prognosis. Triple Negative (TN) and Her2-type breast cancers benefited most from neoadjuvant chemotherapy with higher frequency of pCR. CONCLUSION: HER2-type and TN BC are correlated with best response to NAC. A statistically significant correlation between radiological images and definitive histological examination was not observed.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Terapia Neoadjuvante , Neoplasias da Mama/diagnóstico por imagem , Intervalo Livre de Doença , Feminino , Humanos , Imunofenotipagem , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
5.
Crit Rev Oncol Hematol ; 145: 102855, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927455

RESUMO

Triple-negative breast cancer (TNBC) is defined as a type of breast cancer with lack of expression of estrogen receptor (ER), progesterone receptor (PR) and HER2 protein. The tumorigenesis is not likely to be driven by hormonal or HER2 pathway. In comparison to other types of breast cancer, TNBC stands out for its aggressive behavior, more prone to early recurrence. Historically, TNBC has been considered a disease with poor response to molecular target therapy, requiring better validation of biomarkers. Recent issues related to tumor heterogeneity have been widely discussed suggesting the subdivision of TNBC into different molecular subtypes. Through a complete research on the main published trials databases and platforms of ongoing clinical studies, the current manuscript was carried out in order to present a critical view of the role of immunohistochemical and molecular biomarkers for the prognosis and response prediction of TNBC to traditional therapy and new molecular target agents.


Assuntos
Biomarcadores Tumorais , Neoplasias de Mama Triplo Negativas , Biomarcadores Tumorais/análise , Humanos , Prognóstico , Receptor ErbB-2 , Receptores Estrogênicos , Receptores de Progesterona , Neoplasias de Mama Triplo Negativas/diagnóstico
6.
Toxicol Lett ; 319: 22-30, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31689473

RESUMO

Cadmium (Cd) has estrogen-like activities in breast cancer; it acts as a metalloestrogen in humans. Prospective cohort studies of Cd and breast cancer risk suggest a significant relationship between increased Cd intake and cancer incidence, with more pronounced effects for estrogen receptor α (ERα)-positive breast cancers. However, a recent systematic review with the highest level of evidence demonstrated no such relationship in post-menopausal women. Thus, the reported effects of Cd in pre- and post-menopausal ERα-positive breast cancers are inconsistent. MCF-7 human breast cancer cells normally exhibit growth through estradiol-triggered ERα signaling; however, the MCF-7 cells cultured in estrogen-deprived conditions for a long time (∼ 6 months) eventually result in LTED cells that can be used to utilize to study the proliferation of ERα-positive breast cancer cells obtained from post-menopausal women. Our results showed that unlike MCF-7 cells, LTED cells showed estradiol-independent growth because of constitutively activated ERα. Moreover, Cd (∼10 nM) stimulated ERα signaling in MCF-7 cells and ERα-expressing LTED cells, but not in LTED cells; in ERα-expressing LTED cells, this effect was reversed by ICI 182,780 (an ERα antagonist). Furthermore, in comparison with MCF-7 cells, the LTED cells expressed very low levels of G protein-coupled estrogen receptor 1 (GPER1), a membrane ER capable of stimulating the estrogenic activity of Cd. These findings suggest that the estrogenic action of Cd may be suppressed in LTED cells, and potentially in post-menopausal breast cancer.


Assuntos
Cloreto de Cádmio/toxicidade , Receptor alfa de Estrogênio/metabolismo , Estrogênios/biossíntese , Estrogênios/deficiência , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Neoplasias da Mama/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Antagonistas de Estrogênios/farmacologia , Feminino , Humanos , Células MCF-7
8.
Ecotoxicol Environ Saf ; 188: 109918, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31753310

RESUMO

Hormonal regulation controls mammary gland (MG) development. Therefore some hormone-related factors can disrupt the early phases of MGs development, making the gland more susceptible to long term modifications in its response to circulating hormones. Endocrine disruptors, such as bisphenol A (BPA), are able to cause alterations in hormone receptor expression, leading to changes in the cell proliferation index, which may expose the tissue to neoplastic alterations. Thus, we evaluated the variations in hormone receptor expression in the MG of 6-month old Mongolian gerbils exposed to BPA and 17ß estradiol during the perinatal period. Receptors for estrogen alpha (ERα), beta (ERß), progesterone (PGR), prolactin (PRL-R), and co-localization of connexin 43 (Cx43) and ERα in gerbils were analyzed, and serum concentrations of estradiol and progesterone were assessed. No alterations in body, liver, and ovary-uterus complex weights were observed. However, there was an increase in epithelial ERα expression in the 17ß estradiol (E2) group and in PGR in the BPA group. Although immunohistochemistry did not show alterations in ERß expression, western blotting revealed a decrease in this protein in the BPA group. PRL-R was more present in epithelial cells in the vehicle control (VC), E2, and BPA groups in comparison to the intact control group. Cx43 was more frequent in E2 and BPA groups, suggesting a protective response from the gland against possible malignancy. Serum concentration of estradiol reduced in VC, E2, and BPA groups, confirming that alterations also impacts steroid levels. Consequently, perinatal exposure to BPA and the reference endogenous estrogen, 17ß estradiol, are able to increase the tendency of endocrine disruption in MG in a long term manner, since repercussions are observed even 6 months after exposure.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Estradiol/toxicidade , Glândulas Mamárias Animais/efeitos dos fármacos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Animais , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Feminino , Gerbillinae , Glândulas Mamárias Animais/embriologia , Glândulas Mamárias Animais/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
9.
Sci Total Environ ; 701: 134818, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31706213

RESUMO

Although an increasing body of evidence suggests that triclocarban, a phenyl ether classified as a contaminant of emerging concern, presents a risk to development, there is limited data available on the potential interplay of triclocarban with the developing mammalian nervous system. This study was aimed to investigate the impact of environmentally pervasive chemical triclocarban on autophagy and estrogen receptor-mediated signaling pathways in mouse neurons. The study showed that triclocarban impaired autophagy and disrupted estrogen receptor signaling in mouse embryonic neurons in primary culture. Triclocarban used at environmentally relevant concentrations inhibited the mRNA and protein expression of ESR1 and GPER1 but not ESR2. The triclocarban-induced decrease in the expression of estrogen receptors was supported by the colocalization of the receptors in mouse neurons and corresponded to hypermethylation of the Esr1 and Gper1 genes. Selective antagonists increased the effects of triclocarban, which suggests that the neurotoxic effects of triclocarban, in addition to decreasing estrogen receptor expression, are mediated via inhibition of the neuroprotective capacity of the receptors. Furthermore, Becn1 and Atg7 siRNAs potentiated the caspase-3-dependent effect of triclocarban, which points to triclocarban-induced impairment of autophagy. Indeed, triclocarban dysregulated the expression of autophagy-related genes, and caused a time-dependent inhibition of the mRNA expression of Becn1, Map1lc3a, Map1lc3b, Nup62, and Atg7, which was correlated with a decrease in the protein levels of MAP1LC3B, BECN1 and autophagosomes, but not NUP62 protein level which was increased. Intriguingly, the Esr1 and Gper1 siRNAs did not affect the level of autophagosomes, suggesting that the triclocarban-induced impairment of autophagy is independent of the triclocarban-induced disruption of estrogen receptor signaling in mammalian neurons. Because our data provided evidence that triclocarban has the capacity to impair autophagy and disrupt estrogen receptor signaling in brain neurons at an early developmental stage, we postulate to categorize the compound as a neurodevelopmental risk factor.


Assuntos
Anti-Infecciosos Locais/toxicidade , Carbanilidas/toxicidade , Receptores Estrogênicos/metabolismo , Animais , Metilação de DNA , Camundongos , Neurônios
11.
J Cancer Res Clin Oncol ; 146(2): 315-327, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31865530

RESUMO

PURPOSE: To investigate the interaction between Wnt/ß-catenin and estrogen signaling pathways in endometrial cancer (EC). METHODS: 119 women were involved in this study, including 65 women with histologically confirmed EC and 54 healthy women as a control group. Serum protein levels of Dkk1 were measured using ELISA. Protein expression levels of Dkk1, ß-catenin, ER-ß isoforms (ß1, ß2, ß5), and ER-α were tested in paraffin-embedded tissues using IHC. Gene expression levels of Dkk1, CTNNB, ESR1, and ESR2 were tested in fresh tumorous and normal endometrium tissues using RT-PCR. RESULTS: EC patients had significantly higher serum levels of Dkk1 protein compared with healthy women. Dkk1 and ß-catenin showed different expression pattern in tumor cells compared to it in normal cells at the protein level but not at the gene level. Protein expression levels of ERß2 and ERα were significantly lower in tumor cells compared with tumor-adjacent normal cells. Increased protein expression levels of ERα were associated with favorable clinicopathological features and better overall survival rate (OS). Protein expression levels of ERα were correlated with protein expression levels of Dkk1 and cytoplasmic ß-catenin. The association between ERα expression levels and OS was no more significant when tested in regard to Dkk1- and cytoplasmic ß-catenin expression levels. CONCLUSIONS: Our data demonstrated that Wnt/ß-catenin and estrogen signaling systems are dysregulated in EC showing; for the first time, a potential crosstalk between certain components of these two pathways, which in turn has affected the specificity of these molecules in disease characteristics. Understanding the signaling networks in EC is crucial in designing clinical trials to evaluate the efficacy of molecular-targeted agents and providing more successful therapies in the future.


Assuntos
Neoplasias do Endométrio/metabolismo , Receptores Estrogênicos/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Pessoa de Meia-Idade
12.
Ecotoxicol Environ Saf ; 188: 109875, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706244

RESUMO

Previous works showed that chronic exposure to Aroclor 1254 disrupted glucose homeostasis and induced insulin resistance in male mice. To further observe the different effects of Aroclor 1254 exposure on the pancreatic α-cells and ß-cells, male mice were exposed to Aroclor 1254 (0, 0.5, 5, 50, 500 µg/kg) for 60 days, the pancreas was performed a histological examination. The results showed that the percentage of apoptosis cell (indicated by TUNEL assay) was increased in both α-cells and ß-cells, as the Aroclor 1254 dose was increased; the proliferation (indicated by PCNA expression) rate of ß-cells was elevated while that of α-cells was not affected, resulting in an increased ß-cell mass and a decreased α-cell mass in a dose-depend manner. The number of Pdx-1 positive ß-cells was significantly increased whereas that of Arx positive α-cells was markedly decreased, indicating an enhanced ß-cell neogenesis and a weakened α-cell neogenesis. The drastically reduction of serum testosterone levels in all the treatments suggested an anti-androgenic potency of Aroclor 1254. The up-regulation of estrogen receptors (ERα and ERß) and androgen receptor in ß-cells might be responsible for the increased ß-cell mass and neogenesis.


Assuntos
Antitireóideos/toxicidade , Células Secretoras de Glucagon/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Secretoras de Glucagon/metabolismo , Células Secretoras de Glucagon/patologia , Proteínas de Homeodomínio/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Receptores Androgênicos/metabolismo , Receptores Estrogênicos/metabolismo , Testosterona/sangue , Transativadores/metabolismo , Fatores de Transcrição/metabolismo
13.
Life Sci ; 242: 117186, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862454

RESUMO

AIMS: This study was aimed to investigate the role of GSDME-mediated pyroptosis in cardiac injury induced by Doxorubicin (DOX), and to evaluate the role of BH3-only protein Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (Bnip3) in regulation of DOX-induced pyroptosis. MAIN METHODS: HL-1 cardiomyocytes and C57BL/6J mice were treated by DOX to establish DOX-induced cardiotoxicity in vitro and in vivo models, respectively. Cell transfection was applied to regulate the expression of caspase-3, GSDME and Bnip3. Western blot was used for measuring expression of protein level. LDH-cytotoxicity assay was used to detect the LDH release. The Flow cytometry analysis was used to detect the cell death. Echocardiography was used to determine the cardiac function. HE staining was used for observing pathological feature of heart tissues. KEY FINDINGS: Our results showed that GSDME-mediated pyroptosis was involved in DOX-induced cardiotoxicity in vivo. We showed that HL-1 cardiomyocytes exposed to DOX exhibited morphological features of pyroptosis in vitro. We also showed that DOX induced activation of caspase-3 and eventually triggered GSDME-dependent pyroptosis, which was reduced by the silence or inhibitor of caspase-3. We further showed that knockdown of GSDME inhibited DOX-induced cardiomyocyte pyroptosis in vitro. Finally, DOX increased the expression of Bnip3, whereas silencing of Bnip3 blunted cardiomyocyte pyroptosis induced by DOX, which was regulated through caspase-3 activation and GSDME cleavage. SIGNIFICANCE: Our findings revealed a novel pathway that cardiomyocyte pyroptosis is regulated through Bnip3-caspase-3-GSDME pathway following DOX treatment, suggesting that Bnip3-dependent pyroptosis may offer a novel therapeutic strategy to reduce cardiotoxicity induced by DOX.


Assuntos
Caspase 3/metabolismo , Doxorrubicina/farmacologia , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Receptores Estrogênicos/metabolismo , Animais , Western Blotting , Ecocardiografia , Citometria de Fluxo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
14.
Int J Cancer ; 146(2): 341-351, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30851122

RESUMO

Cadmium, due to its estrogen-like activity, has been suspected to increase the risk of breast cancer; however, epidemiological studies have reported inconsistent findings. We conducted a case-control study (4,059 cases and 4,059 matched controls) nested within the E3N French cohort study to estimate the risk of breast cancer associated with long-term exposure to airborne cadmium pollution, and its effect according to molecular subtype of breast cancer (estrogen receptor negative/positive [ER-/ER+] and progesterone receptor negative/positive [PR-/PR+]). Atmospheric exposure to cadmium was assessed using a Geographic Information System-based metric, which included subject's residence-to-cadmium source distance, wind direction, exposure duration and stack height. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Overall, there was no significant association between cumulative dose of airborne cadmium exposure and the risk of overall, premenopausal and postmenopausal breast cancer. However, by ER and PR status, inverse associations were observed for ER- (ORQ5 vs. Q1 = 0.63; 95% CI: 0.41-0.95, ptrend = 0.043) and for ER-/PR- breast tumors (ORQ4 vs. Q1 = 0.62; 95% CI: 0.40-0.95, ORQ5 vs. Q1 = 0.68; 95% CI: 0.42-1.07, ptrend = 0.088). Our study provides no evidence of an association between exposure to cadmium and risk of breast cancer overall but suggests that cadmium might be related to a decreased risk of ER- and ER-/PR- breast tumors. These observations and other possible effects linked to hormone receptor status warrant further investigations.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Neoplasias da Mama/epidemiologia , Cádmio/efeitos adversos , Adulto , Idoso , Poluição do Ar/estatística & dados numéricos , Mama/patologia , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Pessoa de Meia-Idade , Pós-Menopausa , Pré-Menopausa , Estudos Prospectivos , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Fatores de Risco
15.
Int J Cancer ; 146(2): 352-362, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30861567

RESUMO

Risk of second primary malignancy (SPM) is increasing. We aimed to assess the incidence and related risk factors of SPM among breast cancer (BC) patients from this nested case-control study using the SEER database. BC patients with SPM were identified as the case group and SPM-free patients were defined as the control group. Propensity score matching of cases with controls by the year of the first primary BC diagnosis was conducted at the ratio of 1:5, and 97,242 BC patients were enrolled from 1998 to 2013 after the matching. The incidence of SPM in BC patients stratified by age groups and cancer sites was compared to the general population using the adjusted standardized incidence ratio (SIR) and the risk factors for SPM were examined using Cox proportional hazard regressions. Our study showed BC patients had excess risk for SPM than the general population (adjusted SIR for all cancer sites = 12.94, p < 0.001) and the incidence of SPM among them decreased with age. The risk of SPM was significantly related to the following demographical and clinical variables: age (40-59 vs. 18-39, HR = 1.33; 60-79 vs. 18-39, HR = 2.39; ≥80 vs. 18-39, HR = 2.84), race (black vs. white, HR = 1.12), histological type (lobular BC vs. ductal BC, HR = 1.15), radiotherapy (HR = 1.33), marital status (married vs. single, HR = 0.88) and estrogen receptor status (positive vs. negative, HR = 0.85). Consistent results were found in subgroup analysis stratified by contralateral-breast SPMs and nonbreast SPMs.


Assuntos
Neoplasias da Mama/terapia , Mastectomia Segmentar/efeitos adversos , Segunda Neoplasia Primária/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Radioterapia Adjuvante/estatística & dados numéricos , Receptores Estrogênicos/metabolismo , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Adulto Jovem
16.
Pan Afr Med J ; 34: 67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819783

RESUMO

Introduction: Breast cancer is among the most common cancers among women in most of Africa. However, features of histologically confirmed breast cancers presenting in specific regional populations is limited. Our study describes the clinic-pathologic features of invasive breast cancer diagnosed in women undergoing biopsy for a clinically apparent mass in Senegal, West Africa. Methods: A prospective cohort of 522 Senegalese women presenting consecutively to Dantec Hospital (University of Dakar Tumor Institute) with a breast mass were included in the study cohort. Demographic data was collected by survey and 197 (37.7%) core needle biopsy-confirmed invasive breast cancers available for review were subsequently centrally reviewed at the University of Washington in Seattle to further to characterize the pathologic features and to perform immunohistochemistry for ER/PR and HER2. Results: Seventy six (76.1%) of the 522 Senegalese women presenting for biopsy of a clinically apparent breast mass were diagnosed with invasive breast cancer. The average age of a woman with invasive cancer was 46 years old, and most (83%) presented with Stage III or IV disease. The predominant histologic subtype among the 197 biopsy-confirmed cancers was invasive ductal carcinoma (98%), with few cases of invasive lobular carcinoma (2%). Cancers were classified into four clinically relevant treatment IHC groups by combined ER/PR status and HER2 status as follows: ER-/PR-, HER2- (n=92; 46.7%), ER-/PR-, HER2+ (n=20; 10.1%), ER+/PR+, HER2- (n=76; 38.6%) and ER+/PR+, HER2+ (n=9; 4.6%). Age at time of diagnosis was similar between these four subgroups although more HER2 positive cases were pre-menopausal (p=0.05). Stage of disease at presentation differed by IHC group (p=0.008), with HER2+ cancers significantly more likely to present with stage IV disease than other IHC groups, including ER-/PR-, HER2-. There were no significant differences between groups by age group, ethnicity, place of residence or birth, or parity. Conclusion: Our analysis of breast cancer cases in Senegal shows a distribution of clinically relevant IHC groups like that seen in the few prior studies of breast cancer in West Africa, with higher frequencies of triple negative cancers than in most United States and European populations. Mean age at presentation, delayed presentation, and genetic/regional risk factors likely influence these differences. A better understanding of the frequencies of the pathologic features of breast cancers in the West African population may help guide future genetic studies as well as appropriate clinical management of breast cancer in these populations.


Assuntos
Neoplasias da Mama/patologia , Pré-Menopausa , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Biópsia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Senegal/epidemiologia , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/epidemiologia
18.
Arkh Patol ; 81(6): 41-48, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31851191

RESUMO

OBJECTIVE: To characterize endometrial structural and functional state and receptivity in women with hysteromyoma (HM) and chronic endometritis (CE) in infertile couples. MATERIAL AND METHODS: A total of 130 patients who had HM and/or CE in an infertile couple were examined. Group 1 included 64 women with HM and CE; Group 2 consisted of 24 patients with HM; group 3 comprised 42 patients with EC. A control group included endometrial biopsy specimens from 20 healthy women planning a pregnancy. RESULTS: Patients with HM and CE were found to develop endometrial dysfunction. Its structural signs were damage to the endometrial surface epithelium; intense stromal fibrosis with the high expression of type III and IV collagens; dysregulated processes of high angiogenesis; impaired maturation of pinopodia by the implantation window; high estrogen receptor (ER) expression in the nuclei of endometrial glandular and stromal cells; low progesterone receptor (PR) expression; and impaired secretory endometrial transformation. CONCLUSION: HM concurrent with CE is responsible for endometrial dysfunction. Its structural manifestations are mainly associated with CE.


Assuntos
Endometrite , Infertilidade Feminina , Leiomioma , Neoplasias Uterinas , Doença Crônica , Implantação do Embrião , Endométrio , Feminino , Humanos , Gravidez , Receptores Estrogênicos
19.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4905-4911, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872599

RESUMO

The study aimed to illuminate the role of G protein coupled estrogen receptor( GPER) and its mediated PI3 K/AKT signaling pathway in cryptotanshinone( CPT) induced apoptosis of breast cancer SKBR-3 cells,which is GPER positive and ER negative.The apoptosis rate of SKBR-3 cells was tested by Annexin V-FITC/PI staining and apoptosis effector caspase-3 was determined by Western blot. The key proteins in PI3 K/AKT signaling pathway mediated by GPER were detected by Western blot and immunofluorescence technique. Meanwhile,the agonist G1 and antagonist G15 of GPER and antagonist LY294002 of PI3 K were employed in the test to further clarify the effect of GPER and PI3 K/AKT pathway. The results indicated that the apoptosis rate was increased from 4. 7% to46. 1% and 69. 0% after treatment with 0,5,10 µmol·L~(-1) CPT for 48 h( P<0. 01). The expression of PI3 K,AKT and p-AKT were inhibited( P<0. 05 or P<0. 01),while caspase-3 level increased obviously after treatment with CPT( P<0. 01). Importantly,inhibitory effect of PI3 K/AKT signaling pathway by CPT was further enhanced by G1 and attenuated by G15. LY294002 also induced a further inhibition of expression of AKT and p-AKT. The mean fluorescence intensity of AKT and p-AKT could be decreased by CPT. Furthermore,CPT could downregulate GPER expression in SKBR-3 cells( P<0. 01),which could be inhibited by G1 and enhanced by G15.In conclusion,CPT could induce the apoptosis of ER negative and GPER positive breast cancer SKBR-3 cells and the molecular mechanism is related to its regulatory effect of GPER and its mediated PI3 K/AKT signaling pathway.


Assuntos
Neoplasias da Mama , Medicamentos de Ervas Chinesas , Receptores Estrogênicos , Apoptose , Humanos , Proteínas Proto-Oncogênicas c-akt , Receptores Acoplados a Proteínas-G , Transdução de Sinais
20.
Cell Physiol Biochem ; 53(5): 805-819, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31670920

RESUMO

BACKGROUND/AIMS: Despite effective therapeutic strategies for treating hormone receptor-positive (HR+) breast cancer, resistance to endocrine therapy that is either de novo or acquired still occurs. We investigated epidermal growth factor receptor (EGFR) as a therapeutic target for overcoming endocrine resistance in HR+ breast cancer models. METHODS: Using clinical data from 2,166 patients who had HR+ breast tumors and received tamoxifen, we analyzed survival rates. Levels of mRNA and protein expression were analyzed by real-time PCR and western blotting, respectively. Cell viability was analyzed by MTT assays and anchorage-independent growth by soft agar colony-formation assays. Efficacy of tamoxifen and/or gefitinib was analyzed using orthotopic xenograft mouse models. RESULTS: EGFR expression was significantly associated with more advanced stage and higher grade. EGFR expression was different in luminal A-like (Lum A, 1.3%) versus luminal B-like (Lum B, 11.4%) subtypes. On multivariate analyses for survival Lum B subtype EGFR+ tumors showed a hazard ratio (HR) of 5.22 (95% CI, 1.29-21.15, P = 0.020) for overall survival (OS) and HR of 2.91 (95% CI, 1.35-6.28, P = 0.006) for disease-free survival (DFS). Levels of EGFR inversely correlated with ER-α expression. Basal ER-α level was completely blocked by TGFA or EGF treatment. With TGFA pretreatment, ER+ breast cancer cells were resistant to 4-hydroxytamoxifen (4-OHT). Conversely, downregulation of ER-α by TGFA was reversed by gefitinib with recovered sensitivity to 4-OHT. Tumorigenicity of EGFR and ER+ breast cancer cells were significantly decreased by combined tamoxifen and gefitinib. CONCLUSION: Aberrant EGFR expression was associated with poor prognosis in ER+ breast cancers, especially the Lum B subtype. Loss of ER by EGFR activation induced tamoxifen resistance. Therefore, EGFR could be a therapeutic target for overcoming recurrence of ER+ breast cancer with high EGFR expression.


Assuntos
Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Adulto , Idoso , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/mortalidade , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Receptor ErbB-2/antagonistas & inibidores , Receptores Estrogênicos/metabolismo , Taxa de Sobrevida , Tamoxifeno/análogos & derivados , Tamoxifeno/química , Tamoxifeno/farmacologia
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