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1.
Int J Cancer ; 146(1): 150-160, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31173341

RESUMO

The Combined Aerobic and Resistance Exercise (CARE) Trial compared different types and doses of exercise performed during breast cancer chemotherapy. Here, we report the longer-term follow-up of patient-reported outcomes, health-related fitness and exercise behavior at 6, 12 and 24 months postintervention. A multicenter trial in Canada randomized 301 breast cancer patients initiating chemotherapy to thrice weekly, supervised exercise consisting of a standard dose of 25-30 min of aerobic exercise (STAN; n = 96), a higher dose of 50-60 min of aerobic exercise (HIGH; n = 101) or a combined dose of 50-60 min of aerobic and resistance exercise (COMB; n = 104) performed for the duration of chemotherapy (median of 17 weeks). Primary outcomes were patient-reported outcomes including quality of life, cancer-related symptoms and psychosocial outcomes. Secondary outcomes were objective health-related fitness (assessed at 12 months only) and self-reported exercise behavior. A total of 269 (89.4%) participants completed patient-reported outcomes at all three follow-up time points and 263 (87.4%) completed the health-related fitness assessment at 12-month follow-up. COMB was significantly superior to (i) STAN for sleep quality at 6-month follow-up (p = 0.027); (ii) HIGH for upper body muscular endurance at 12-month follow-up (p = 0.020); and (iii) HIGH for meeting the resistance exercise guideline at 6-month follow-up (p = 0.006). Moreover, self-reported meeting of the combined exercise guideline during follow-up was significantly associated with better patient-reported outcomes and health-related fitness. Performing combined exercise during and after breast cancer chemotherapy may result in better longer-term patient-reported outcomes and health-related fitness compared to performing aerobic exercise alone.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Exercício , Medidas de Resultados Relatados pelo Paciente , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Qualidade de Vida
2.
Genes Dev ; 34(3-4): 179-193, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31879358

RESUMO

The GATA-type zinc finger transcription factor TRPS1 has been implicated in breast cancer. However, its precise role remains unclear, as both amplifications and inactivating mutations in TRPS1 have been reported. Here, we used in vitro and in vivo loss-of-function approaches to dissect the role of TRPS1 in mammary gland development and invasive lobular breast carcinoma, which is hallmarked by functional loss of E-cadherin. We show that TRPS1 is essential in mammary epithelial cells, since TRPS1-mediated suppression of interferon signaling promotes in vitro proliferation and lactogenic differentiation. Similarly, TRPS1 expression is indispensable for proliferation of mammary organoids and in vivo survival of luminal epithelial cells during mammary gland development. However, the consequences of TRPS1 loss are dependent on E-cadherin status, as combined inactivation of E-cadherin and TRPS1 causes persistent proliferation of mammary organoids and accelerated mammary tumor formation in mice. Together, our results demonstrate that TRPS1 can function as a context-dependent tumor suppressor in breast cancer, while being essential for growth and differentiation of normal mammary epithelial cells.


Assuntos
Neoplasias da Mama/fisiopatologia , Carcinogênese/genética , Diferenciação Celular/genética , Células Epiteliais/citologia , Proteínas Repressoras/metabolismo , Animais , Neoplasias da Mama/genética , Caderinas/genética , Sobrevivência Celular/genética , Cromatina/genética , Cromatina/metabolismo , Modelos Animais de Doenças , Feminino , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Humanos , Glândulas Mamárias Humanas/crescimento & desenvolvimento , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/genética , Complexo Mi-2 de Remodelação de Nucleossomo e Desacetilase/metabolismo , Camundongos , Ligação Proteica/genética , Proteínas Repressoras/genética , Transdução de Sinais/genética
3.
Pharm Res ; 37(1): 7, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31845095

RESUMO

PURPOSE: Antidepressants like the serotonin reuptake inhibitors (SRIs) are often used concomitantly with tamoxifen (e.g. for treatment of depression). This may lead to an additional prolongation of the QTc-interval, with an increased risk of cardiac side effects. Therefore we investigated whether there is a drug-drug interaction between tamoxifen and SRIs resulting in a prolonged QTc-interval. METHODS: Electrocardiograms (ECGs) of 100 patients were collected at steady state tamoxifen treatment, with or without concomitant SRI co-medication. QTc-interval was manually measured and calculated using the Fridericia formula. Primary outcome was difference in QTc-interval between tamoxifen monotherapy and tamoxifen concomitantly with an SRI. RESULTS: The mean QTc-interval was 12.4 ms longer when tamoxifen was given concomitantly with an SRI (95% CI:1.8-23.1 ms; P = 0.023). Prolongation of the QTc-interval was particularly pronounced for paroxetine (17.2 ms; 95%CI:1.4-33.0 ms; P = 0.04), escitalopram (12.5 ms; 95%CI:4.4-20.6 ms; P < 0.01) and citalopram (20.7 ms; 95%CI:0.7-40.7 ms; P = 0.047), where other agents like venlafaxine did not seem to prolong the QTc-interval. None of the patients had a QTc-interval of >500 ms. CONCLUSIONS: Concomitant use of tamoxifen and SRIs resulted in a significantly higher mean QTc-interval, which was especially the case for paroxetine, escitalopram and citalopram. When concomitant administration with an SRI is warranted venlafaxine is preferred.


Assuntos
Antidepressivos de Segunda Geração/farmacologia , Antineoplásicos Hormonais/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Inibidores de Captação de Serotonina/efeitos adversos , Tamoxifeno/efeitos adversos , Idoso , Antidepressivos de Segunda Geração/efeitos adversos , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/complicações , Citalopram/farmacologia , Feminino , Humanos , Síndrome do QT Longo/induzido quimicamente , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/farmacologia , Tamoxifeno/farmacologia
4.
Rev. bras. cir. plást ; 34(4): 531-538, oct.-dec. 2019. ilus, tab
Artigo em Inglês, Português | LILACS | ID: biblio-1047921

RESUMO

O linfoma anaplásico de grandes células associado ao implante de mama (Breast Implant Associated Anaplastic Large Cell Lymphoma - BIA-ALCL) é uma doença maligna recentemente descoberta, rara e possivelmente associada aos implantes mamários texturizados. Essa revisão da literatura teve como objetivo trazer novas atualizações acerca da epidemiologia, fisiopatologia e fatores de risco para desenvolvimento do BIAALCL. Foi realizado o levantamento de dados do período de dezembro de 2018 a fevereiro de 2019, através das bases de dados PUBMED, LILACS e Scielo sendo selecionados 10 artigos publicados entre 2016 e 2018. Foi encontrada uma incidência variando entre 2,8:100.000 a 1:3 milhões de pacientes com implantes mamários. Os dados coletados corroboram para a teoria de que não há uma relação direta de causa e efeito entre os implantes mamários, mormente os texturizados, e o desenvolvimento do BIA-ALCL, podendo esses ser considerados somente como fatores de risco e não agentes causadores. A teoria fisiopatológica mais aceita é a de que os implantes mamários com maior área de superfície levariam a formação de maior biofilme por maior adesão bacteriana gerando inflamação crônica mais proeminente, levando ao gatilho para a transformação maligna das células T. As informações explicitadas nessa revisão devem auxiliar na ampliação de estudos acerca da doença e criação de políticas públicas para a prevenção e diagnóstico precoce de tal enfermidade. Pelos dados encontrados há necessidade de que cirurgiões plásticos realizem acompanhamento mais próximo de seus pacientes, assim como orientem os pacientes antes das cirurgias sobre a existência da doença.


Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a newly discovered and rare cancer possibly associated with textured breast implants. This literature review investigates its epidemiology, pathophysiology, and risk factors. PubMed, LILACS, and SciELO databases were searched from December 2018 to February 2019, and 10 articles published between 2016 and 2018 were selected. The incidence of BIA-ALCL ranged from 2.8:100,000 to 1:3 million breast implants. The obtained data corroborate the hypothesis that there is no direct cause and effect relationship between breast implants, especially textured implants, and BIA-ALCL, and these implants can be considered risk factors but not causative factors. The most accepted hypothesis on disease pathophysiology is that breast implants with larger surface areas may promote bacterial adhesion and biofilm formation, leading to severe chronic inflammation, triggering the malignant transformation of T cells. This review provides knowledge on BIA-ALCL and helps develop and implement public policies for disease prevention and timely diagnosis. The data highlight that long-term follow up is necessary and that surgeons should advise patients of the potential risk of developing BIA-ALCL before performing the implant surgery.


Assuntos
Humanos , História do Século XXI , Linfoma não Hodgkin , Neoplasias da Mama , Linfoma de Células T , Revisão , Linfoma Anaplásico de Células Grandes , Implantes de Mama , Neoplasias da Mama/fisiopatologia , Doença de Hodgkin/fisiopatologia , Linfoma de Células T/fisiopatologia , Linfoma Anaplásico de Células Grandes/cirurgia , Linfoma Anaplásico de Células Grandes/fisiopatologia , Implantes de Mama/estatística & dados numéricos
5.
Medicine (Baltimore) ; 98(44): e17708, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689803

RESUMO

The aim of this study was to assess the effect of preoperative sleep quality on acute postoperative pain in breast cancer patients.The Pittsburgh Sleep Quality Index questionnaire (PSQI) was used to assess the overall sleep status of women scheduled for unilateral modified radical mastectomy in the past month. Based on the responses, patients were allocated to good sleep group or poor sleep group. Postoperatively, acute pain was assessed using the numerical rating score in the first 24 hours; in addition, the requirement of analgesics and the incidence of postoperative complications were recorded.A total of 108 breast surgery patients were enrolled. Based on the PSQI results, 55 (51%) patients were allocated to poor sleep group and 53 (49%) to good sleep group. Pain scores were similar in the 2 groups at the end of surgery (P = .589); however, poor sleep group reported higher postoperative pain scores than the good sleep group at 2 (P = .002), 6 (P < .001), 12 (P < .001), and 24 (P = .002) hours after surgery. The incidence of severe pain in the poor sleep group was higher than that in the good sleep group (27% vs 8%, P = .018), and the ratio of participants who required rescued analgesics was greater in the poor sleep group (52% vs 22%, P = .002). In addition, patients with poor sleep quality had more postoperative complications and longer hospital stay.In this study, breast cancer patients with poor preoperative sleep quality reported more severe postoperative pain, required more analgesics, experienced more complications, and had longer hospital stay.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia/efeitos adversos , Dor Pós-Operatória/etiologia , Distúrbios do Início e da Manutenção do Sono/complicações , Sono , Adolescente , Adulto , Idoso , Analgésicos/uso terapêutico , Neoplasias da Mama/complicações , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Período Pré-Operatório , Estudos Prospectivos , Fatores de Risco , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Adulto Jovem
6.
BMC Complement Altern Med ; 19(1): 273, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638975

RESUMO

BACKGROUND: Curcumin is known for its multitude of medicinal properties, including anti-cancer and migrastatic activity. Efforts to overcome poor bioavailability, stability, and side effects associated with the higher dose of curcumin has led to the development of newer derivatives of curcumin. Thus, the focus of this study is to screen novel curcumin derivatives, namely ST03 and ST08, which have not been reported before, for their cytotoxicity and migrastatic property on cancer cells. METHODS: Anti-cancer activity of ST03 and ST08 was carried out using standard cytotoxicity assays viz., LDH, MTT, and Trypan blue on both solid and liquid cancer types. Flow cytometric assays and western blotting was used to investigate the cell death mechanisms. Transwell migration assay was carried out to check for migrastatic properties of the compounds. RESULTS: Both the compounds, ST03 and ST08, showed ~ 100 fold higher potency on liquid and solid tumour cell lines compared to its parent compound curcumin. They induced cytotoxicity by activating the intrinsic pathway of apoptosis in the breast (MDA-MB-231) and ovarian cancer cell lines (PA-1) bearing metastatic and stem cell properties, respectively. Moreover, ST08 also showed inhibition on breast cancer cell migration by inhibiting MMP1 (matrix metalloproteinase 1). CONCLUSION: Both ST03 and ST08 exhibit anti-cancer activity at nanomolar concentration. They induce cell death by activating the intrinsic pathway of apoptosis. Also, they inhibit migration of the cancer cells by inhibiting MMP1 in breast cancer cells.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama/fisiopatologia , Movimento Celular/efeitos dos fármacos , Curcumina/química , Curcumina/farmacologia , Neoplasias Ovarianas/fisiopatologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Metaloproteinase 1 da Matriz/metabolismo , Estrutura Molecular , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo
7.
Gait Posture ; 74: 162-168, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31525654

RESUMO

BACKGROUND: Decreased muscular strength and poorer postural stability impact the physical function of breast cancer survivors (BCS) and increases their risk of falls. Gait assessment, particularly in the backward direction, is often used as an indicator of fall risk in several populations. However this information is unknown in BCS. RESEARCH QUESTION: What are the differences in forward, backward, and accelerated forward walking in BCS in comparison to individuals without a prior cancer diagnosis? METHODS: 17 postmenopausal BCS (mean age: 58.5 (8.5) years) and 17 age-matched women without a prior cancer diagnosis (mean age: 59.11 (5.55) years) completed 5 trials each of forward, backward, and fast forward walking conditions. Absolute (Means) and variability (Coefficient of variation) estimates were obtained for spatio-temporal gait parameters. Lower body, upper body and handgrip strengths were measured. RESULTS: For absolute estimates of gait, significant group main effects indicated that BCS had 7% shorter step length (P = 0.019) and 8% slower gait speed (P = 0.048). For variability estimates of gait, there was a significant interaction for stance time (P = 0.035). BCS had greater stance time variability during forward and fast forward conditions, but lesser variability during backward condition. Averaged across all the conditions, BCS had 38% greater step length variability (P = 0.043), 50% greater gait speed variability (P = 0.028), and 28.5% greater single support time variability (P = 0.004). Averaged across both the groups, all the variables except for swing time variability were significantly different among the conditions (all P< = 0.013). BCS also had significantly reduced upper body strength (P = 0.036). SIGNIFICANCE: Slower and shorter steps while walking both forwards and backwards could be indicative of a more cautious gait strategy by BCS. Also, BCS possibly focused on controlling spatial parameters during forward walking but temporal parameters while backward walking. Whether these alterations are related to an increased fall risk within BCS needs to be determined.


Assuntos
Neoplasias da Mama/fisiopatologia , Marcha/fisiologia , Caminhada/fisiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular/fisiologia , Equilíbrio Postural/fisiologia , Velocidade de Caminhada/fisiologia
8.
BMC Complement Altern Med ; 19(1): 211, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409331

RESUMO

BACKGROUND: Breast cancer is the leading cause of cancer-related death in women worldwide. Although traditional Chinese medicine (TCM) is commonly used by patients with breast cancer, little is known about TCM prescriptions for breast cancer. This study investigated the effects of a new TCM formula, T33, comprising Radix Kansui, Rheum rhabarbarum, Paeonia lactiflora, Jiangbanxia, and Zhigancao on breast cancer cells in vitro and in vivo. METHODS: To evaluate the effects of T33 on human breast cancer, HMEpiC, MDA-MB231 and MCF-7 cells were treated with different concentrations of T33 and then analyzed using MTT and Transwell migration assays. To elucidate the involvement of autophagy in the T33-induced death of MDA-MB231 and MCF-7 cells, immunofluorescence staining with LC3-II-specific antibodies was performed. Tumor xenografts were generated by subcutaneously injecting either MDA-MB231 or MCF-7 cells into BALB/c nude mice to determine the effects of T33 on these cell lines in vivo. RESULTS: The experimental results revealed that 0.1 mg/mL, 0.5 mg/mL, 2.5 mg/mL, 5 mg/mL and 10 mg/mL T33 significantly inhibited the proliferation and invasion of MDA-MB231 and MCF-7 cells. Moreover, significant autophagy was observed in MDA-MB231 and MCF-7 cells in the presence of 2.5 mg/mL, 5 mg/mL and 10 mg/mL T33. An animal study further revealed that both low (200 mg/kg) and high (600 mg/kg) doses of T33 inhibited the proliferation of xenografted breast cancer cells in BALB/c nude mice. CONCLUSION: These findings demonstrate for the first time that T33 has potential in the treatment of breast cancer owing to its antiproliferative effects and induction of autophagy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Animais , Autofagia , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
9.
J Agric Food Chem ; 67(36): 10042-10047, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31422658

RESUMO

The present study compared the growth-inhibitory effects of four common branched chain fatty acids (BCFAs) found in beef and dairy fats including iso 15:0, anteiso 15:0, iso 17:0, and anteiso 17:0. MCF-7 human breast cancer cells were exposed for 72 h to media containing increasing doses (50 to -400 µM) of the four BCFA. Cell viability was not affected by any of the BCFA treatments at doses less than 200 µM. Culturing cells with 200 µM of iso-15:0 or iso-17:0 reduced cell viability by 27 ± 2.8 and 43 ± 8.3% at 24 h, 35 ± 4.6 and 49 ± 9.1% at 48 h, and 44 ± 6.8 and 57 ± 8.8% at 72 h posttreatment. In contrast, culturing cells with 200 µM of anteiso-15:0 or anteiso-17:0 did not affect cell viability for any durations tested. The incorporation of iso 15:0 and iso 17:0 into cells (19.1 ± 1.3 and 21.2 ± 1.4 µmol/mg protein, respectively) was greater (P < 0.01) than that of anteiso 15:0 and anteiso 17:0 (11.8 ± 0.7 and 13.8 ± 0.8 µmol/mg protein, respectively). Iso-15:0 and iso-17:0 downregulated (P < 0.01) the expression of antiapoptotic Bcl-2 (0.71 ± 0.6-fold and 0.64 ± 0.09-fold, respectively) and upregulated (P < 0.01) the expression of proapoptotic Bax (1.72 ± 0.14-fold and 2.15 ± 0.24-fold, respectively) compared to the control, whereas their corresponding anteiso isomers did not affect the expression of any apoptosis-related genes. Our findings suggest that the branching structure influences anticarcinogenic effects of BCFAs, with iso being more potent than anteiso.


Assuntos
Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/fisiopatologia , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Inibidores do Crescimento/química , Inibidores do Crescimento/metabolismo , Carne/análise , Animais , Neoplasias da Mama/genética , Bovinos , Proliferação de Células , Sobrevivência Celular , Feminino , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
10.
J Clin Nurs ; 28(23-24): 4560-4571, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31469461

RESUMO

AIMS AND OBJECTIVES: To examine and compare the differences in symptoms and symptom clusters between postmenopausal women with early-stage breast cancer who did and did not receive chemotherapy prior to aromatase inhibitor (AI) therapy. BACKGROUND: Women with breast cancer often experience multiple concurrent symptoms during AI therapy. The burden of symptoms prior to AI is associated with nonadherence to cancer treatment. To date, few studies have comprehensively explored the symptoms and symptom clusters occurring prior to AI therapy. DESIGN: Secondary analysis of a prospective repeated-measures study. METHODS: The sample comprised postmenopausal women (N = 339) with breast cancer who would receive AI therapy with or without chemotherapy. We collected information on 48 symptoms after surgery or chemotherapy but before AI therapy using different symptom assessment tools. Mann-Whitney U tests were used to compare the differences in the severity of symptoms between groups. Exploratory factor analysis (EFA) was conducted to determine symptom clusters. This study followed STROBE guidelines. RESULTS: The most severe symptoms among women with breast cancer prior to AI therapy were breast sensitivity, unhappy with the appearance of my body, general aches and pain, joint pain and muscle stiffness. Women who received chemotherapy prior to AI therapy experienced significantly higher severity of 22 symptoms than women who did not receive chemotherapy. Through EFA seven distinct symptom clusters were revealed in both groups: cognitive, musculoskeletal, psychological, vasomotor, weight, sexual and urinary, with additional gastrointestinal symptom cluster been identified in women who received chemotherapy. CONCLUSIONS: This study indicates the presence of symptoms among women with breast cancer prior to AI therapy, with higher severity of symptoms and greater number of symptom clusters for women who received chemotherapy. RELEVANCE TO CLINICAL PRACTICE: Nurses should assess and be aware of symptoms and symptom clusters existed prior to AI therapy and manage them in advance.


Assuntos
Anastrozol/efeitos adversos , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Idoso , Anastrozol/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/complicações , Neoplasias da Mama/fisiopatologia , Estudos de Casos e Controles , Feminino , Terapia de Reposição Hormonal , Humanos , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Pós-Menopausa , Estudos Prospectivos , Síndrome
11.
Am J Chin Med ; 47(5): 1149-1170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31311297

RESUMO

Three-dimensionally (3D) cultured tumor cells (spheroids) exhibit more resistance to therapeutic agents than the cells cultured in traditional two-dimensional (2D) system (monolayers). We previously demonstrated that arsenic disulfide (As2S2) exerted significant anticancer efficacies in both 2D- and 3D-cultured MCF-7 cells, whereas 3D spheroids were shown to be resistant to the As2S2 treatment. L-buthionine-(S, R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, has been regarded to be a potent candidate for combinatorial treatment due to its GSH modulation function. In the present study, we introduced BSO in combination with As2S2 at a low concentration to investigate the possible enhancing anticancer efficacy by the combinatorial treatment on 2D- and 3D-cultured MCF-7 cells. Our results presented for the first time that the combination of As2S2 and BSO exerted potent anticancer synergism in both MCF-7 monolayers and spheroids. The IC50 values of As2S2 in combinatorial treatment were significantly lower than those in treatment of As2S2 alone in both 2D- and 3D-cultured MCF-7 cells (P<0.01, respectively). In addition, augmented induction of apoptosis and enhanced cell cycle arrest along with the regulation of apoptosis- and cell cycle-related proteins, as well as synergistic inhibitions of PI3K/Akt signals, were also observed following co-treatment of As2S2 and BSO. Notably, the combinatorial treatment significantly decreased the cellular GSH levels in both 2D- and 3D-cultured MCF-7 cells in comparison with each agent alone (P<0.05 in each). Our results suggest that the combinatorial treatment with As2S2 and BSO could be a promising novel strategy to reverse arsenic resistance in human breast cancer.


Assuntos
Antineoplásicos/farmacologia , Arsenicais/farmacologia , Neoplasias da Mama/fisiopatologia , Butionina Sulfoximina/farmacologia , Sulfetos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Técnicas de Cultura de Células , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Humanos , Células MCF-7 , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo
12.
BMC Cancer ; 19(1): 653, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269914

RESUMO

BACKGROUND: Anthracycline-based chemotherapy is associated with reduced cardiorespiratory fitness in breast cancer patients. High intensity interval training (HIIT) induces greater benefits on cardiorespiratory fitness than moderate continuous aerobic exercise in patients with heart failure. The study purpose was to determine whether a HIIT intervention is a feasible exercise strategy for breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty women were randomized to either HIIT or non-exercise control group (CON). Participants performed a maximal cycling fitness test to measure peak power output during maximal oxygen uptake (VO2max). The HIIT group participated in an 8-week HIIT intervention occurring 3 times weekly. Feasibility was calculated by computing (1) the average weekly minutes of HIIT over 8 weeks and (2) the number of sessions attended and multiplied by 100 (percentage of sessions). The intervention was considered feasible if more than 50% of participants completed both an average of 70% of weekly minutes (63/90 min) and attended 70% exercise sessions (17/24 sessions). RESULTS: Participants were 46.9 ± 9.8 (mean ± SD) years old, diagnosed with clinical stage II (30%) or III (63%) breast cancer. The average weekly minutes of exercise completed was 78 ± 5.1 out of 90 min. Twelve of 15 participants met both feasibility criteria, attending 19.2 ± 2.1 out of 24 sessions (82.3%). VO2max was maintained (19.7 ± 8.7 to 19.4 ± 6.6 ml/kg/min) in HIIT group (p = 0.94) while there was a significant decrease in VO2max (18.7 ± 7.1 to 16.1 ± 6.0 ml/kg/min) in CON group from baseline to 8 weeks (p = 0.001). CONCLUSIONS: HIIT is a feasible exercise intervention to maintain VO2max in breast cancer patients receiving anthracycline-based chemotherapy. TRIAL REGISTRATION: The protocol and informed consent were approved by the institutional IRB (HS-12-00227) and registered ( ClinicalTrials.gov NCT02454777; date of registration: May 272,015).


Assuntos
Antraciclinas/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Treinamento Intervalado de Alta Intensidade , Consumo de Oxigênio , Aptidão Física , Antraciclinas/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto
13.
Int J Mol Sci ; 20(13)2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31277289

RESUMO

Atomic force microscopy (AFM) combined with fluorescence microscopy has been used to quantify cytomechanical modifications induced by resveratrol (at a fixed concentration of 50 µM) in a breast cancer cell line (MCF-7) upon temporal variation. Cell indentation methodology has been utilized to determine simultaneous variations of Young's modulus, the maximum adhesion force, and tether formation, thereby determining cell motility and adhesiveness. Effects of treatment were measured at several time-points (0-6 h, 24 h, and 48 h); longer exposures resulted in cell death. Our results demonstrated that AFM can be efficiently used as a diagnostic tool to monitor irreversible morpho/nano-mechanical changes in cancer cells during the early steps of drug treatment.


Assuntos
Neoplasias da Mama/fisiopatologia , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Módulo de Elasticidade/efeitos dos fármacos , Microscopia de Força Atômica/métodos , Resveratrol/farmacologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Células MCF-7 , Fenômenos Mecânicos/efeitos dos fármacos , Resveratrol/uso terapêutico
14.
Comput Math Methods Med ; 2019: 3041250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31281408

RESUMO

Residual cancer burden (RCB) has been proposed to measure the postneoadjuvant breast cancer response. In the workflow of RCB assessment, estimation of cancer cellularity is a critical task, which is conventionally achieved by manually reviewing the hematoxylin and eosin- (H&E-) stained microscopic slides of cancer sections. In this work, we develop an automatic and direct method to estimate cellularity from histopathological image patches using deep feature representation, tree boosting, and support vector machine (SVM), avoiding the segmentation and classification of nuclei. Using a training set of 2394 patches and a test set of 185 patches, the estimations by our method show strong correlation to those by the human pathologists in terms of intraclass correlation (ICC) (0.94 with 95% CI of (0.93, 0.96)), Kendall's tau (0.83 with 95% CI of (0.79, 0.86)), and the prediction probability (0.93 with 95% CI of (0.91, 0.94)), compared to two other methods (ICC of 0.74 with 95% CI of (0.70, 0.77) and 0.83 with 95% CI of (0.79, 0.86)). Our method improves the accuracy and does not rely on annotations of individual nucleus.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/fisiopatologia , Diagnóstico por Computador , Processamento de Imagem Assistida por Computador/métodos , Algoritmos , Núcleo Celular/patologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Modelos Lineares , Reconhecimento Automatizado de Padrão , Probabilidade , Curva ROC , Reprodutibilidade dos Testes , Máquina de Vetores de Suporte , Fluxo de Trabalho
15.
J Surg Oncol ; 120(3): 518-526, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31168844

RESUMO

BACKGROUND: The axillary-approach pedicled descending branch latissimus dorsi (LD) mini-flap presents clear benefits in repairing partial mastectomy defects. This study assessed the functional and esthetic outcomes of this flap compared with conventional breast-conserving surgery (BCS). METHODS: From October of 2015 to March of 2017, patients with early breast cancer were enrolled and assigned to the LD group or conventional BCS (CCS) group according to the need of using the pedicled descending branch LD mini-flap for volume replacement. Muscle strength and range of motion (ROMs) of bilateral shoulders, a disabilities of the arm, shoulder and hand (DASH) questionnaire, and an esthetic evaluation were conducted in all patients at 1 year after surgery. RESULTS: Thirty-two patients were assigned in the LD group, and 28 in the CCS group. There was no significant difference in muscle strength, ROMs of the shoulder or DASH scores between LD and CCS groups. The results of esthetic survey also revealed a similarly high level of esthetics in both groups. Donor-site seroma occurred in three patients in the LD group, and no other complication was observed. CONCLUSIONS: The pedicled descending branch LD mini-flap enabled larger excision with favorable esthetics, minimal functional impairment, low rate of complications, and high level of satisfaction.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Segmentar/métodos , Retalhos Cirúrgicos , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Mastectomia Segmentar/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ombro/fisiologia , Adulto Jovem
16.
Neoplasma ; 66(5): 746-755, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31169019

RESUMO

MiR-21-5p has been identified as an oncogene to enhance human tumor progression. Here, we explored the mechanism by which miR-21-5p regulated the progression and paclitaxel (PTX) resistance in drug-resistant breast cancer (BC) cell lines. qRT-PCR assays were used to assess the expression levels of miR-21-5p and PDCD4 mRNA, and western blotting was used to detect PDCD4 protein level in PTX-resistant BC cell lines. Dual-luciferase reporter assay was used to observe the interaction between miR-21-5p and PDCD4 in PTX-resistant BC cell lines. Cell proliferation ability and IC50 values of PTX were measured by CCK-8 assay, cell cycle progression and apoptosis were determined with flow cytometry analysis, and cell migration and invasion capacities were analyzed using Transwell assay. Xenograft mice assay was used to validate the important role of miR-21-5p as a regulator on PTX-resistance BC cells growth in vivo. Then, we found that miR-21-5p was upregulated and PDCD4 was downregulated in BC tissues and PTX-resistant BC cell lines. MiR-21-5p silencing or PDCD4 overexpression ameliorated PTX resistance and inhibited the progression in PTX-resistant BC cell lines. Moreover, PDCD4 was demonstrated to be a direct target of miR-21-5p. MiR-21-5p exerted its regulatory effect by PDCD4 in PTX-resistant BC cell lines. Additionally, miR-21-5p silencing inhibited tumor growth in vivo. Therefore, our study demonstrated that miR-21-5p silencing ameliorated PTX resistance and inhibited the progression in PTX-resistant BC cell lines at least partly by targeting PDCD4, providing miR-21-5p as an effective therapeutic target for PTX-resistant BC treatment.


Assuntos
Proteínas Reguladoras de Apoptose , Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , MicroRNAs , Paclitaxel , Proteínas de Ligação a RNA , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , MicroRNAs/metabolismo , Paclitaxel/farmacologia , Proteínas de Ligação a RNA/metabolismo
17.
J Biochem Mol Toxicol ; 33(8): e22339, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31157481

RESUMO

Breast cancer (BC) is one of the most widespread malignancies in women worldwide. Breast cancer is mainly classified into a few key molecular subtypes in accordance with hormone and growth factor receptor expression, etc. In spite of numerous advances in the remedy of breast cancer, the development of metastatic disease remains an untreatable and repeated basis of cancer death for women. Preclinical and clinical studies of immunotherapy in cancer remedy have been in progress for the past quite a few decades by an effort to accelerate, augment, and modulate the immune system to spot and devastate cancer cells. Advancement of cancer immunotherapy is rapidly increasing with eminent and most interesting therapy compared to other therapy like targeted therapy, cytotoxic chemotherapy, radiation as well as surgery. Cancer immunotherapy, also known as biological therapy, which denotes the controlling and by means of the patient's own immune system to goal the cancer cells rather than using an extrinsic therapy. In that way, focusing of cancer immunotherapy developing mediators that stimulates or enhances the immune system's recognition and destroying the cancer cells. This review describes a holistic outlook and deeper understanding of the biology of immunotherapy within the system of tumor microenvironment of breast cancer that improve clinical research and constructive impact on the study conclusion.


Assuntos
Neoplasias da Mama/terapia , Imunoterapia/métodos , Neoplasias da Mama/etiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Ensaios Clínicos como Assunto , Feminino , Humanos , Metástase Neoplásica
18.
Breast ; 46: 126-135, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158651

RESUMO

OBJECTIVES: Traditional methods measuring physical activity (PA) may misrepresent breast cancer survivors (BCSs) and low-socioeconomic status (SES) groups. This study identifies PA-levels, routines and experiences among BCSs, in general and by SES, and explores whether a mixed-methods approach might unveil diversities of PA in BCS across SES. MATERIALS AND METHODS: 250 BCSs referred to postoperative radiation therapy in 2007-2008 participated in a longitudinal follow-up study examining health-related quality-of-life and late-effects. Subsample-data on SES and PA were collected by questionnaires (n = 52), activity-logs (n = 52) and interviews (n = 37). Parallel mixed analyses were conducted, in combination with sequential, full-sample analyses of questionnaires and contrasting case analyses of logs and interviews. RESULTS: Dependent on which measurement used, 23%, 35%, 54% and 63% of BCSs met PA guidelines. Questionnaire-data revealed no significant differences in PA levels between SES groups. Log-data showed more PA bouts in high-SES BCSs, but no difference in min/week across SES. Neighbourhood walking was preferred, while scheduled exercise was rare. Interview-data added that PA was medicating, normatively described and accompanied by unfulfilled ambitions, particularly in low-SES BCSs. Balancing duties and activities was demanding. PA constraints were similar across groups. Domestic PA was important in low-SES, while high-SES BCSs described more energy. CONCLUSION: Although PA levels among BCSs were similar across SES and equal to PA in the general population, SES differences became evident when measured by activity-logs and as stated in interviews. Future follow-up programs for BCSs could benefit from expanding the PA perspectives, thus better meet the needs of different SES groups.


Assuntos
Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Exercício/psicologia , Idoso , Neoplasias da Mama/fisiopatologia , Sobreviventes de Câncer/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Qualidade de Vida , Classe Social , Inquéritos e Questionários , Fatores de Tempo
19.
Mol Med Rep ; 20(2): 1057-1064, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173245

RESUMO

Breast cancer (BC) is a common malignancy among women and the leading cause of female cancer mortality worldwide. In recent years, increasing evidence has shown that long non­coding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) in human cancer and that they are involved in many biological processes, including proliferation, migration, apoptosis and invasion. In the present study, the biological function and molecular mechanism of ataxin 8 opposite strand (ATXN8OS) in BC tissue and cell lines were investigated. It was found that ATXN8OS was markedly up­regulated in BC tissue and cell lines, and that its level of overexpression was inversely linked with the overall survival rate of patients with BC. Knockdown of ATXN8OS inhibited proliferation, viability and invasion in the human MCF7 and MDA­MB­231 BC cell lines. In addition, microRNA­204 (miR­204) was negatively associated with the expression of ATXN8OS in BC tissues and cell lines. A luciferase assay demonstrated a direct binding site for miR­204 within ATXN8OS, and inhibition of miR­204 stimulated the tumour­promoting effect of ATXN8OS on BC cells. In conclusion, the present study suggested that ATXN8OS acts as a tumour promoter by sequestering miR­204 during the development of BC, therefore providing a mechanistic insight which may facilitate the diagnosis and treatment of BC.


Assuntos
Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Células MCF-7 , Invasividade Neoplásica , Oncogenes
20.
Breast Cancer Res Treat ; 177(2): 477-485, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31236810

RESUMO

PURPOSE: The purpose of this study was to determine the effects of an 8-week high-intensity interval training (HIIT) intervention on vascular endothelial function, measured as brachial artery flow-mediated dilation (baFMD), and vascular wall thickness measured by carotid intima media thickness (cIMT) in breast cancer patients undergoing anthracycline-based chemotherapy. METHODS: Thirty women were randomized to either HIIT or non-exercise control groups (CON). The HIIT group participated in an 8-week HIIT intervention occurring three times per week on a cycle ergometer. The CON group was offered the HIIT intervention after 8 weeks. baFMD was measured from the brachial artery diameter at baseline (D0) and 1 min after cuff deflation (D1); percent change was calculated by measuring brachial artery diameter after cuff deflation relative to the baseline [baFMD = (D1 - D0)/D0 × 100]. The cIMT was obtained from the posterior wall of common carotid artery 10 mm below the carotid bulb. Paired t test and repeated measures ANCOVA were performed to assess changes in baFMD and cIMT. RESULTS: At baseline, the HIIT (n = 15) and CON (n = 15) groups did not differ by age (46.9 ± 9.8 years), BMI (31.0 ± 7.5 kg/m2), and blood pressure (123.4 ± 16.8/72.3.9 ± 5.6 mmHg). Post-exercise, baFMD significantly increased [4.3; 95% confidence interval (CI): (1.5, 7.0), p = 0.005] in HIIT versus CON group. cIMT did not significantly change [0.003, 95% CI - 0.004, 0.009), p = 0.40] in HIIT group, while IMT significantly increased from baseline to post-intervention (0.009, 95% CI 0.004, 0.010, p = 0.003) in CON group. CONCLUSION: This study may suggest that HIIT improved vascular endothelial function and maintained wall thickness in breast cancer patients undergoing anthracycline-based chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02454777.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/terapia , Espessura Intima-Media Carotídea , Endotélio Vascular/fisiopatologia , Terapia por Exercício , Treinamento Intervalado de Alta Intensidade , Adulto , Antraciclinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/diagnóstico , Terapia Combinada , Terapia por Exercício/métodos , Feminino , Treinamento Intervalado de Alta Intensidade/métodos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Resultado do Tratamento
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