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1.
Anticancer Res ; 42(1): 253-261, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969732

RESUMO

BACKGROUND/AIM: Many experimental studies have suggested the importance of thyroid hormones in breast cancer (BC) morphogenesis. The aim of this study was to evaluate the association of thyroid hormone levels in serum of patients with primary BC with morphological presentations of the disease in pathological specimens and prognosis. PATIENTS AND METHODS: We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum thymidine kinase 1 activity and examined their relation to pathological features and prognosis of 158 patients with primary BC. RESULTS: We found a significant positive association of serum FT3 level with the presence of carcinoma in situ component (CIS) (p=0.032) and its size (p=0.047), with the presence (p=0.022) and the number of multifocal/multicentric tumors (MMTs) (p=0.002), as well as with increased proliferative activity in terms of serum thymidine kinase 1 (p=0.002). Moreover, we report that each 1.0 unit rise of FT3/FT4 ratio×10 was associated with an odds ratio of 1.77 (95% confidence interval=1.17-3.30, p=0.007), 1.97 (95% confidence interval=1.17-2.67, p=0.010) and 1.56 (95% confidence interval=1.02-2.37, p=0.039) for the detection of patients with CIS, MMTs and lymphovascular invasion, respectively, after adjusting for age. We did not find statistically significant associations of serum TSH level with breast cancer`s parameters. A Cox regression survival analysis identified serum FT3 level >5.95 pmol/l as a risk factor for BC recurrence (relative risk=2.65, p=0.017), a finding that retained significance in a multivariate model (relative risk=2.52, p=0.027). CONCLUSION: The FT3/FT4 ratio is a valuable parameter predicting the presence of CIS, MMTs and lymphovascular invasion in pathological specimens. An elevated serum FT3 level is associated with the presence of CIS, MMTs, increased proliferative activity and poor prognosis.


Assuntos
Neoplasias da Mama/sangue , Carcinoma in Situ/sangue , Recidiva Local de Neoplasia/sangue , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Proliferação de Células/genética , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Timidina Quinase/sangue , Testes de Função Tireóidea , Glândula Tireoide/patologia , Hormônios Tireóideos/genética , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
2.
Nutrients ; 13(12)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34959982

RESUMO

Breast cancer (BC) treatments induce vitamin D (VD) insufficiency and bone metabolism changes, resulting in osteoporosis and skeletal morbidity risk. We report the results of a bicentric phase II trial (ClinicalTrials.gov Identifier: NCT04091178) on the safety and efficacy of high-dose oral VD supplementation for VD deficiency correction in 44 patients with early BC treated with adjuvant chemotherapies. Patients received one dose of 100,000 IU 25-OH VD every 3 weeks from day 1 of cycle 1 to day 1 of cycle 5. The primary endpoint was the percentage of patients achieving serum 25-OH VD concentration normalization on day 1 of cycle 6 (D1C6). Secondary endpoints were safety, VD and calcium parameters at baseline and during chemotherapy, and identification of predictive biomarkers of VD normalization on D1C6. On D1C6, 21 patients (47.7%, 95% CI: 33.0-62.8) achieved VD normalization. No VD-related clinical toxicity was reported. However, 13 patients (29.5%) presented asymptomatic grade 1 hypercalciuria, leading to interruption of the high-dose oral VD supplementation in 10, followed by a rapid reduction in serum VD concentration. No baseline clinical factor was predictive of VD normalization on D1C6. This high-dose VD supplementation appears safe and efficient in patients with early BC receiving adjuvant chemotherapy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/efeitos adversos , Suplementos Nutricionais , Deficiência de Vitamina D/terapia , Vitamina D/administração & dosagem , Adulto , Idoso , Biomarcadores , Neoplasias da Mama/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/induzido quimicamente
3.
Bull Cancer ; 108(11S): 11S46-11S54, 2021 Dec.
Artigo em Francês | MEDLINE | ID: mdl-34969515

RESUMO

The tumor biopsy remains essential for breast cancer diagnosis and characterization. Indeed, the treatment is decided according to histological subtype, and according to the presence of targetable molecular alterations. Notably, the presence of hormone receptors, ERBB2 hyperexpression or the existence of PIK3CA or ESR1 mutations are among the alterations commonly investigated. But these biological characteristics are determined only partially by tumor biopsy, due to tumor heterogeneity or tumor plasticity that happens spontaneously or under treatment. Liquid biopsy, and in particular circulating tumor DNA and circulating tumor cells, is a non-invasive method to identify and characterize the presence of cancer in the blood. The aim of this review is to determine the value of liquid biopsy to enhance or replace the data provided by a tumor biopsy.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , DNA Tumoral Circulante/sangue , Biópsia Líquida , Neoplasias da Mama/sangue , Neoplasias da Mama/química , Classe I de Fosfatidilinositol 3-Quinases/genética , Receptor alfa de Estrogênio/genética , Feminino , Amplificação de Genes , Genes erbB-2 , Humanos , Mutação , Células Neoplásicas Circulantes/patologia , Receptor ErbB-2/análise
4.
Nutrients ; 13(12)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34959876

RESUMO

Breast cancer (Bca) is the most common type of cancer among women worldwide, and oxidative stress caused by adjuvant treatment may be decreased by antioxidant intake. The aim of this study is to investigate the associations between Dietary antioxidant Capacity (DaC) and oxidation and antioxidant biomarkers in women undergoing adjuvant treatment (AT) for Bca. This prospective study had a sample of 70 women (52.2 ± 10.7 y). DaC (mmol/g) was calculated using nutritional data obtained from a Food Frequency Questionnaire, and blood was collected to measure the oxidation and antioxidant biomarkers at baseline (T0), and after AT (T1). Carbonylated protein levels were inversely associated with DaC at T1 (p = 0.004); women showed an increased risk of having increment on lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS), and decrement on ferric reducing antioxidant power (FRAP) and reduced glutathione after AT, in response to lowered DaC (p < 0.05). Carbonylated proteins, TBARS and FRAP levels remained stable between the periods for women at the 3rd DaC tertile at T1, differentiating them from those at the 1st tertile, who showed negative changes in these biomarkers (p < 0.04). DaC may be beneficial for women undergoing AT for Bca, since it promoted a reduction in oxidative stress.


Assuntos
Antioxidantes/administração & dosagem , Neoplasias da Mama/sangue , Dieta/métodos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Biomarcadores/sangue , Neoplasias da Mama/terapia , Quimioterapia Adjuvante/efeitos adversos , Inquéritos sobre Dietas , Ingestão de Alimentos/fisiologia , Feminino , Glutationa/sangue , Humanos , Peróxidos Lipídicos/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Carbonilação Proteica/efeitos dos fármacos , Radioterapia Adjuvante/efeitos adversos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
5.
Int J Mol Sci ; 22(24)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34948336

RESUMO

Malignant cells differ from benign ones in their metabolome and it is largely unknown whether this difference is reflected in the metabolic profile of their microvesicles (MV), which are secreted into the blood of cancer patients. Here, they are present together with MV from the various blood and endothelial cells. Harvesting MV from 78 breast cancer patients (BC) and 30 controls, we characterized the whole blood MV metabolome using targeted and untargeted mass spectrometry. Especially (lyso)-phosphatidylcholines and sphingomyelins were detected in a relevant abundance. Eight metabolites showed a significant discriminatory power between BC and controls. High concentrations of lysoPCaC26:0 and PCaaC38:5 were associated with shorter overall survival. Comparing BC subtype-specific metabolome profiles, 24 metabolites were differentially expressed between luminal A and luminal B. Pathway analysis revealed alterations in the glycerophospholipid metabolism for the whole cancer cohort and in the ether lipid metabolism for the molecular subtype luminal B. Although this mixture of blood-derived MV contains only a minor number of tumor MV, a combination of metabolites was identified that distinguished between BC and controls as well as between molecular subtypes, and was predictive for overall survival. This suggests that these metabolites represent promising biomarkers and, moreover, that they may be functionally relevant for tumor progression.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/metabolismo , Vesículas Extracelulares/metabolismo , Metaboloma , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/sangue , Feminino , Humanos , Espectrometria de Massas , Metabolômica , Pessoa de Meia-Idade , Fosfatidilcolinas/sangue , Esfingomielinas/sangue , Adulto Jovem
6.
Nutrients ; 13(10)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34684340

RESUMO

Dietary pattern (DP) and its relationship with disease biomarkers have received recognition in nutritional epidemiology investigations. However, DP relationships with adipokines (i.e., adiponectin and leptin) among breast cancer survivors remain unclear. Therefore, we assessed relationships between DP and high-molecular weight (HMW) adiponectin and leptin concentration among breast cancer survivors. This cross-sectional study involved 128 breast cancer survivors who attended the oncology outpatient clinic at two main government hospitals in the East Coast of Peninsular Malaysia. The serum concentration of HMW adiponectin and leptin were measured using enzyme-linked immunosorbent assay (ELISA) kits. A reduced rank regression method was used to analyze DP. Relationships between DP with HMW adiponectin and leptin were examined using regression models. The findings show that with every 1-unit increase in the 'energy-dense, high-SFA, low-fiber' DP z-score, there was a reduction by 0.41 µg/mL in HMW adiponectin which was independent of age, BMI, education level, occupation status, cancer stage, and duration since diagnosis. A similar relationship with leptin concentration was not observed. In conclusion, the 'energy-dense, high-saturated fat and low-fiber' DP, which is characterized by high intake levels of sugar-sweetened drinks and fat-based spreads but low intake of fruits and vegetables, is an unhealthy dietary pattern and unfavorable for HMW adiponectin concentration, but not for leptin. These findings could serve as a basis in developing specific preventive strategies that are tailored to the growing population of breast cancer survivors.


Assuntos
Adiponectina/sangue , Neoplasias da Mama/sangue , Sobreviventes de Câncer , Fibras na Dieta/farmacologia , Ácidos Graxos/farmacologia , Leptina/sangue , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Regressão
7.
Nutrients ; 13(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34684483

RESUMO

Breast cancer (BC) is a major public health concern and substantial research has shown that adhering to a healthy dietary pattern, such as the Mediterranean Diet (MD), may prevent the onset of cancer and BC relapses. This study aims at specifically investigating the association of MD with circulating dietary-related biomarkers in a cohort of BC survivors. Eighty patients (mean age of 54.9 ± 10.6) with a histologically confirmed diagnosis of BC who had not received any pharmacological or radiotherapy treatment for at least two months were enrolled. Fasting serum lipid-soluble vitamins (retinol, tocopherol), plant pigments (ß-carotene, lutein + zeaxanthin, cryptoxanthin, lycopene), inflammatory and oxidative stress markers (ceruloplasmin; haptoglobin; paraoxonases; reactive oxygen molecule; thiol groups, Ferric reducing antioxidant power), and cardiometabolic parameters (body mass index (BMI); glucose; insulin; HOMA-IR; total cholesterol; LDL-cholesterol; HDL-cholesterol; triglycerides) were analyzed. Adherence to the MD was assessed through the Mediterranean Diet Score (MDS) questionnaire. Fasting blood samples were collected for the evaluation of selected biomarkers. MDS resulted positively correlated with ß-carotene (r 0.331; p < 0.01) and lycopene (r 0.274; p < 0.05) and negatively with retinol (r -0.346; p < 0.05). Among the investigated inflammatory biomarkers, MDS was only correlated with antioxidant capacity (r 0.256; p < 0.05), while none of the investigated cardiometabolic parameters were significantly correlated with this index. The strong significant correlation between ß-carotene and MDS encourages us to consider this pro-vitamin as a putative biomarker to take into account for evaluating the adherence to the MD.


Assuntos
Biomarcadores/sangue , Neoplasias da Mama/sangue , Sobreviventes de Câncer , Dieta Mediterrânea , Mediadores da Inflamação/sangue , Lipídeos/química , Micronutrientes/sangue , Carotenoides/sangue , Estudos de Coortes , Feminino , Humanos , Inflamação/sangue , Pessoa de Meia-Idade , Solubilidade , Vitaminas/sangue
8.
BMC Cancer ; 21(1): 1062, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565331

RESUMO

BACKGROUND: Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC). METHODS: We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: No difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively. CONCLUSIONS: BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Neoplasias da Mama/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteína BRCA2/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/sangue , Fatores de Transcrição de Zíper de Leucina Básica/genética , Mama/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Bases de Dados Factuais , Exossomos/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/genética , Prognóstico , RNA Mensageiro/metabolismo , Receptores Androgênicos/metabolismo , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/sangue , Proteínas Supressoras de Tumor/genética
9.
Clin Immunol ; 232: 108847, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34506945

RESUMO

BACKGROUND: Cancer development is among other factors driven by tumor immune escape and tumor-mediated changes in the immune response. Investigating systemic immune changes may provide important knowledge for the improvement of patient prognosis and treatment opportunities. METHODS: The systemic immune profile of patients with ER-positive breast cancer (n = 22) and healthy controls (n = 30) was investigated based on complete blood counts, flow cytometric analysis of T cell subsets including regulatory T cells (Tregs), and immune assays investigating soluble (s)HLA-G and the cytokine profile in plasma. We further examined the correlation between the immune markers and clinical parameters including tumor size, tumor grade and lymph node involvement. RESULTS: Results indicated that breast cancer patients possessed a higher amount of neutrophils and monocytes and fewer lymphocytes and eosinophils compared with healthy controls. Breast cancer patients had significantly more CD25+CD127low Tregs than controls, and both lymphocyte and Treg numbers were negatively correlated with tumor size. Furthermore, Treg numbers were elevated in grade I tumors compared with grade II tumors and with healthy controls. No difference in sHLA-G levels was observed between patients and controls. Higher levels of IL-6 and TNF-α were observed in breast cancer patients. Cytokine and sHLA-G levels were not associated with clinical parameters. CONCLUSION: The results of this exploratory study contribute to the elucidation of the systemic immune response in breast cancer indicating a potential use of peripheral immune cell counts and Tregs to distinguish patients from healthy controls and as potential diagnostic and prognostic biomarkers to be investigated in future studies.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/sangue , Neoplasias da Mama/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade
10.
Oncology ; 99(11): 740-746, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34515174

RESUMO

INTRODUCTION: It has been suggested that age could influence the treatment-induced side effects and survival time of cancer patients. The influence of age on blood-based biomarkers, acute radiation skin reactions (ARSRs), and survival time of breast cancer patients was analysed. MATERIALS AND METHODS: Two hundred ninety-three individuals, 119 breast cancer patients, and 174 healthy blood donors were included. RESULTS: Before radiotherapy (RT), decreased levels of lymphocytes, interleukin 2, platelet-derived growth factors, and tumour necrosis factor but increased levels of monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, C-reactive protein, and macrophage inflammatory protein 1b (MIP1b) were detected in the patient group. All of the patients developed ARSRs and intensity of ARSRs was inversely related to the MIP1b level before RT. Fifteen out of 119 (13%) patients deceased during follow-up time. No influence of age (≤50 compared to >50 years) on survival time was detected (p = 0.442). Tumour recurrence, found in 11 out of 119 (9%) patients, had impact on survival time of these patients (p < 0.001). CONCLUSIONS: The level of circulating MIP1b before RT was associated with intensity of ARSRs. Tumour recurrence, but not age, was associated with poor survival time. Analysis of circulating MIP1b was low cost, rapid, and could be done in routine laboratory facility. Since RT almost always induces ARSRs, the possibility of using MIP1b as a prognostic biomarker for ARSRs is of interests for further investigation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Recidiva Local de Neoplasia/mortalidade , Radiodermatite/sangue , Radiodermatite/etiologia , Radioterapia Adjuvante/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias da Mama/radioterapia , Proteína C-Reativa/análise , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Contagem de Linfócitos , Linfócitos/metabolismo , Pessoa de Meia-Idade , Monócitos , Neutrófilos/metabolismo , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
PLoS One ; 16(9): e0257704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34555072

RESUMO

Breast cancer (BC) is becoming one of the most prevalent non-infectious disease in low and middle income countries. The steady rise of BC incidence may be related to the different risk factors. Among many, rampant presence of environmental pollutants might be one of the risk factors. Therefore, the aim of this study is to investigate exposure to organochlorine pesticides as a risk factor to breast cancer. A case-control study design was employed among breast cancer patients and non-breast cancer individuals (controls). Blood samples were collected from 100 study participants (50 cases and 50 controls) followed by serum separation, extraction and cleanup using standard analytical procdures. The findings revealed that ten organochlorine pesticides were detected in the serum of the study participants. From the detected organochlorine pesticides, heptachlor was observed at higher concentration for breast cancer patients (6.90±4.37 µg/L) and controls (9.15±3.84 µg/L). Mean serum level of p,p'-DDE, p,p'-DDT, heptachlor, gamma-chlordane, endosulfan, and dibutyl-chlorendate were significantly higher in the serum of breast cancer patients than the controls. From the studied pesticides, p,p'-DDT and gamma-chlordane are significant predictors for BC, while, others are equivocal. A unit increment of the concentration of p,p'-DDT (AOR; 2.03, 95% CI: 1.041-3.969) increased the odds of developing breast cancer by two, while for gamma-chlordane (AOR;3.12, 95% CI; 1.186-8.203) by three. Our study results suggesting that, organochlorines are a risk factors for breast cancer in Ethiopia. Decreasing exposure to such organochlorines might have a significant public health relevance in reducing non-communicable chronic illnesses. Besides, continues monitoring of persistent organic pollutants using body biomarkers is important for disease prevention and device mitigation measures.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/epidemiologia , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Adulto , Neoplasias da Mama/sangue , Neoplasias da Mama/induzido quimicamente , Estudos de Casos e Controles , Clordano/efeitos adversos , Clordano/sangue , DDT/efeitos adversos , DDT/sangue , Diclorodifenil Dicloroetileno/efeitos adversos , Diclorodifenil Dicloroetileno/sangue , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/sangue , Etiópia/epidemiologia , Feminino , Heptacloro/efeitos adversos , Heptacloro/sangue , Humanos , Hidrocarbonetos Clorados/efeitos adversos , Pessoa de Meia-Idade , Praguicidas/efeitos adversos
12.
Biomed Res Int ; 2021: 5473959, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485514

RESUMO

Background: The hypercoagulable status, which forms a vicious cycle with hematogenous metastasis, is a common systemic alteration in cancers. As modeling is a key approach in research, a model which is suitable for studying how the hypercoagulable status promotes hematogenous metastasis in breast cancer is urgently needed. Methods: Based on the tumor-bearing period (TBP) and postoperative incubation period (PIP), 4T1-breast cancer models were constructed to evaluate coagulation and tumor burden to generate multiple linear regression-based lung metastasis prediction formula. Platelets and 4T1 cells were cocultured for 30 min or 24 h in vitro to evaluate the early and late phases of their crosstalk, and then the physical characteristics (concentration and size) and procoagulant activity of the coculture supernatants were assayed. Results: The multiple linear regression model was constructed as log10 (photon number) = 0.147 TBP + 0.14 PIP + 3.303 (TBP ≤ 25 and PIP ≤ 17) to predict lung metastasis. Coculture of platelets and 4T1 cells contributed to the release of extracellular vesicles (EVs) and the development of the hypercoagulable status. Conclusions: In vivo and in vitro hypercoagulable status models were developed to explore the mechanism of hypercoagulable status which is characterized by platelet activation and promotes hematogenous metastasis in breast cancer.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/patologia , Trombofilia/sangue , Trombofilia/patologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Teóricos , Metástase Neoplásica , Ativação Plaquetária
13.
BMC Cancer ; 21(1): 1052, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34563150

RESUMO

BACKGROUND: Breast cancer is the second leading cause of cancer in the world. It is the commonest type of cancer in Ethiopia. Cognitive problems are common among breast cancer patients. The study aimed to assess cognitive functioning and its associated factors among breast cancer patients at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia 2020. METHODS: Institution-based comparative cross-sectional study was conducted. Study subjects were 117 breast cancer patients on chemotherapy and 117 women without breast cancer who volunteered for the study. Data was collected from May-June 2020. The Mini-mental status exam (MMSE) was used to assess cognitive functioning. Data were entered into Epi Data version 4.6.0.2 and analyzed using STATA version 14 software. Univariable and multivariable linear regression model was fitted to identify factors associated with cognitive functioning. A two-tailed p-value less than 0.05 was used to declare statistical significance. RESULTS: Among the total breast cancer patients 41.9% were diagnosed with earlier sage of the diseases (stage I and II), while the rest 58.1% were diagnosed with stage III and stage IV breast cancer. A significant difference in the MMSE score was observed among breast cancer patients and controls (19.76 ± 5.29, 25.18 ± 4.68 p <  0.0001) respectively. In multivariable linear regression analysis being non-breast cancer (Adjusted beta coefficient (Adj.ß.coff). = 3.34, 95% CI (1.92-4.76) p <  0.001), hemoglobin gm/dl (Adj.ß.coff =0.34, 95% CI (0.04-0.63) p = 0.02), and primary education (Adj.ß.coff =2.98 95%CI (1.16-4.96) p = 0.001) secondary level and more education (Adj.ß.coff = 5.47, 95%CI (3.51-7.28) p < 0.001) were significantly associated with MMSE cognitive score. CONCLUSION: Breast cancer patients had lower mean MMSE scores when compared to non-breast cancer women. Higher hemoglobin level and higher level of education increase the MMSE cognitive score. Clinicians should incorporate routine screening of cognitive functioning for breast cancer patients and further study is required to evaluate cognitive impairment among breast cancer patients in Ethiopia.


Assuntos
Neoplasias da Mama/fisiopatologia , Transtornos Cognitivos/diagnóstico , Cognição/fisiologia , Adulto , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Institutos de Câncer , Intervalos de Confiança , Estudos Transversais , Escolaridade , Etiópia , Feminino , Hemoglobina A/análise , Humanos , Modelos Lineares , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Estadiamento de Neoplasias
14.
Radiol Oncol ; 55(3): 292-304, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34384011

RESUMO

BACKGROUND: Circulating tumor cells (CTCs) have become an important biomarker in breast cancer. Different isolation tech-niques based on their biological or physical features were established. Currently, the most widely used methods for visualization after their separation are based on immunofluorescent staining, which does not provide the information on the morphology. MATERIALS AND METHODS: The aim of this study was to evaluate how two different separation techniques affect cell morphology and to analyse cell morphology with techniques used in routine cytopathological laboratory. A direct side-by-side comparison of physical (Parsortix®) and biological (MACS®) separation technique was performed. RESULTS: In the preclinical setting, both isolation techniques retained the viability and antigenic characteristics of MCF7 breast cancer cells. Some signs of degeneration such as cell swelling, cytoplasmic blebs, villous projections and vacuolization were observed. In metastatic breast cancer patient cohort, morphological features of isolated CTCs were dependent on the separation technique. After physical separation, CTCs with preserved cell morphology were detected. After biological separation the majority of the isolated CTCs were so degenerated that their identity was difficult to confirm. CONCLUSIONS: Taken together, physical separation is a suitable technique for detection of CTCs with preserved cell morphology for the use in a routine cytopathological laboratory.


Assuntos
Neoplasias da Mama/patologia , Separação Celular/métodos , Forma Celular , Células Neoplásicas Circulantes/patologia , Corantes Azur , Neoplasias da Mama/sangue , Sobrevivência Celular , Corantes , Feminino , Humanos , Células MCF-7/patologia
15.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445424

RESUMO

Biomarkers for predicting individual response to radiation and for dose verification are needed to improve radiotherapy. A biomarker should optimally show signal fidelity, meaning that its level is stable and proportional to the absorbed dose. miRNA levels in human blood serum were suggested as promising biomarkers. The aim of the present investigation was to test the miRNA biomarker in leukocytes of breast cancer patients undergoing external beam radiotherapy. Leukocytes were isolated from blood samples collected prior to exposure (control); on the day when a total dose of 2 Gy, 10 Gy, or 20 Gy was reached; and one month after therapy ended (46-50 Gy in total). RNA sequencing was performed and univariate analysis was used to analyse the effect of the radiation dose on the expression of single miRNAs. To check if combinations of miRNAs can predict absorbed dose, a multinomial logistic regression model was built using a training set from eight patients (representing 40 samples) and a validation set with samples from the remaining eight patients (15 samples). Finally, Broadside, an explorative interaction mining tool, was used to extract sets of interacting miRNAs. The most prominently increased miRNA was miR-744-5p, followed by miR-4461, miR-34a-5p, miR-6513-5p, miR-1246, and miR-454-3p. Decreased miRNAs were miR-3065-3p, miR-103a-2-5p, miR-30b-3p, and miR-5690. Generally, most miRNAs showed a relatively strong inter-individual variability and different temporal patterns over the course of radiotherapy. In conclusion, miR-744-5p shows promise as a stable miRNA marker, but most tested miRNAs displayed individual signal variability which, at least in this setting, may exclude them as sensitive biomarkers of radiation response.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/radioterapia , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , MicroRNAs/genética , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Fracionamento da Dose de Radiação , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Sequência de RNA , Resultado do Tratamento , Regulação para Cima
16.
Int J Mol Sci ; 22(11)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204158

RESUMO

Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Perfilação da Expressão Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estatísticas não Paramétricas , Adulto Jovem
17.
Int J Cancer ; 149(8): 1605-1618, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34196964

RESUMO

In patients with metastatic breast cancer (MBC), brain metastases (BM) are associated with high morbidity and mortality. However, there is no validated serum biomarker that accurately predicts BM occurrence in these patients, and the role of serum biomarkers for prognosis remains unclear. Here, we evaluated the association of neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1 (UCHL1), glial fibrillary acidic protein (GFAP) and tau serum levels with BM presence and prognosis in patients with MBC. In serum samples from patients with MBC with (n = 100) and without BM (n = 47), we measured the biomarker serum levels using single molecule array (Simoa) technology (Neurology-4-Plex assay). To evaluate their accuracy to identify patients with BM, we determined the receiver operating characteristic curve and the area under the curve (AUC) for each biomarker and calculated their sensitivity and specificity. The median serum levels of NfL, UCHL1, tau and GFAP were significantly higher in patients with BM. The AUC for GFAP (0.82, 95% confidence interval [CI] 0.75-0.88) was significantly higher than those of the other biomarkers considered independently. Using the medians as cutoff values, elevated serum levels of NfL, UCHL1, tau and GFAP were associated with BM in univariate analysis, but only high GFAP levels in multivariate analysis (odd ratio 23.4, 95% CI 6.8-80.5, P < .001). Elevated serum GFAP levels were independently associated with poor outcome. GFAP outperforms NfL, UCHL1 and tau as diagnostic and prognostic factor of BM in patients with MBC. These results must now be validated in an independent cohort of patients.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Proteína Glial Fibrilar Ácida/sangue , Adulto , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/terapia , Neoplasias da Mama/sangue , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida
18.
Sci Rep ; 11(1): 14662, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282214

RESUMO

Blood-based biomarkers reflect systemic inflammation status and have prognostic and predictive value in solid malignancies. As a recently defined biomarker, Pan-Immune-Inflammation-Value (PIV) integrates different peripheral blood cell subpopulations. This retrospective study of collected data aimed to assess whether PIV may predict the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in Turkish women with breast cancer. The study consisted of 743 patients with breast cancer who were scheduled to undergo NAC before attempting cytoreductive surgery. A pre-treatment complete blood count was obtained in the two weeks preceding NAC, and blood-based biomarkers were calculated from absolute counts of relevant cell populations. The pCR was defined as the absence of tumor cells in both the mastectomy specimen and lymph nodes. Secondary outcome measures included disease-free survival (DFS) and overall survival (OS). One hundred seven patients (14.4%) had pCR. In receiver operating characteristic analysis, optimal cut-off values for the neutrophile-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte (PLR), PIV, and Ki-67 index were determined as ≥ 2.34, ≥ 0.22, ≥ 131.8, ≥ 306.4, and ≥ 27, respectively. The clinical tumor (T) stage, NLR, MLR, PLR, PIV, estrogen receptor (ER) status, human epidermal growth factor receptor-2 (HER-2) status, and Ki-67 index were significantly associated with NAC response in univariate analyses. However, multivariate analysis revealed that the clinical T stage, PIV, ER status, HER-2 status, and Ki-67 index were independent predictors for pCR. Moreover, the low PIV group patients had significantly better DFS and OS than those in the high PIV group (p = 0.034, p = 0.028, respectively). Based on our results, pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in predicting pCR in Turkish women with breast cancer who received NAC. However, further studies are needed to confirm our findings.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Inflamação/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Terapia Combinada , Feminino , Humanos , Inflamação/sangue , Inflamação/patologia , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Valor Preditivo dos Testes , Prognóstico , Projetos de Pesquisa , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Microambiente Tumoral/imunologia , Turquia/epidemiologia , Adulto Jovem
19.
Sci Rep ; 11(1): 13630, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34211050

RESUMO

Metastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor-derived cell population, circulating hybrid cells (CHCs), harboring attributes from both macrophages and neoplastic cells, including functional characteristics important to metastatic spread. These disseminated hybrids outnumber conventionally defined circulating tumor cells (CTCs) in cancer patients. It is unknown if CHCs represent a generalized cancer mechanism for cell dissemination, or if this population is relevant to the metastatic cascade. Herein, we detect CHCs in the peripheral blood of patients with cancer in myriad disease sites encompassing epithelial and non-epithelial malignancies. Further, we demonstrate that in vivo-derived hybrid cells harbor tumor-initiating capacity in murine cancer models and that CHCs from human breast cancer patients express stem cell antigens, features consistent with the potential to seed and grow at metastatic sites. Finally, we reveal heterogeneity of CHC phenotypes reflect key tumor features, including oncogenic mutations and functional protein expression. Importantly, this novel population of disseminated neoplastic cells opens a new area in cancer biology and renewed opportunity for battling metastatic disease.


Assuntos
Células Híbridas/patologia , Neoplasias/patologia , Células Neoplásicas Circulantes/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Neoplasias/sangue
20.
J Steroid Biochem Mol Biol ; 212: 105947, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34214604

RESUMO

Conflicting results have been reported on the association of blood vitamin D level with prognosis in women with breast cancer. This meta-analysis aimed to evaluate the association between blood 25-hydroxyvitamin D level and survival outcomes in female breast cancer patients. Two authors independently searched PubMed and Embase databases from their inception to August 25, 2020. Prospective or retrospective cohort studies evaluating the association between blood 25-hydroxyvitamin D level and survival outcomes in women with breast cancer were included. Outcome measures included overall survival (OS), breast cancer-specific survival (BCSS), and disease-free survival (DFS). Twelve studies involving 8574 female breast cancer patients were identified and analyzed. When compared the lowest with the highest category of 25-hydroxyvitamin D level, the pooled adjusted hazard ratio (HR) was 1.57 (95 % confidence interval [CI] 1.35-1.83) for OS, 1.98 (95 % CI 1.55-2.53) for DFS, and 1.44 (95 % CI 1.14-1.81) for BCSS. This meta-analysis indicates that lower blood 25-hydroxyvitamin D level is significantly associated with reduced survival among female breast cancer patients. Additional clinical trials are required to investigate whether vitamin D supplement can improve survival outcomes in these patients.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Vitamina D/análogos & derivados , Vitaminas/sangue , Feminino , Humanos , Vitamina D/sangue
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