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1.
Anticancer Res ; 39(10): 5653-5662, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570463

RESUMO

BACKGROUND/AIM: Factors influencing fulvestrant efficacy may be useful in selecting the optimal treatment regimen for postmenopausal Japanese women with metastatic/recurrent HR-positive, HER2-negative breast cancer. PATIENTS AND METHODS: We retrospectively evaluated progression-free and overall survival (PFS and OS) in 100 fulvestrant-treated patients according to metastatic site. RESULTS: Median PFS was significantly better in patients with non-visceral (bone and regional metastases; 22.8 months) vs. visceral metastasis (lung, liver, and other organs; 8.2 months; p=0.024), although median OS did not differ (p=0.922). Median PFS in patients with lung metastasis (20.8 months) and non-visceral metastasis (22.8 months) were comparable; patients with liver metastasis (6.1 months) and other organ metastases (3.7 months) had worse prognoses. CONCLUSION: Patients with non-visceral metastases had a better prognosis than those with visceral metastases. Fulvestrant induced a longer PFS in patients with non-visceral metastasis, and also in those with lung metastasis without liver or other organ involvement.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Fulvestranto/uso terapêutico , Metástase Neoplásica/prevenção & controle , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Intervalo Livre de Progressão , Receptor ErbB-2/genética , Receptores de Superfície Celular/genética , Estudos Retrospectivos
2.
Anticancer Res ; 39(10): 5741-5745, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570476

RESUMO

BACKGROUND/AIM: Cardiovascular risk factors (CVRFs) predict cardiotoxicity in cancer patients but their role in late cardiac toxicity is less clear. PATIENTS AND METHODS: This was a retrospective analysis of patients treated with anthracyclines (A) and/or trastuzumab (T) and a correlation with early (≤5 years) or late (>5 years) cardiac toxicity, and baseline CVRFs and CVRFs at toxicity time. RESULTS: A total of 610 patients were included, 422 with (Group A) and 188 without (Group B) baseline CVRFs. In group A toxicity incidence was 4.7% with all events during treatment or immediately after [mean onset time 0.7 years (range=0.2-1.6)]. Events rate was 3.2% in group B with all events after five years [mean time onset 6.9 years (range=5.2-7.5)]. All group B patients who developed late cardiac toxicity presented with CVRFs at the time of toxicity not reported before. CONCLUSION: CVRFs could predict late cardiac toxicity and their control should be part of the survivorship program.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiopatias/induzido quimicamente , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
3.
Medicine (Baltimore) ; 98(37): e17135, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517852

RESUMO

RATIONALE: In estrogen receptor-positive HER2-negative (ER+HER2-) metastatic breast cancer, chemotherapy should be offered only to patients who develop endocrine resistance or have a rapid disease progression. However, the correct sequence of chemotherapy administration is still debated. PATIENT CONCERNS: We report the case of a 49-year-old woman with ER+ HER2- metastatic breast cancer who experienced an exceptionally long response to capecitabine administered as second-line therapy following a first-line anthracycline-based chemotherapy. DIAGNOSES: The patient was diagnosed with ER+ HER2- metastatic breast cancer with massive liver involvement and mediastinal lymph nodes metastasis. INTERVENTIONS: This patient was treated with capecitabine 1000 mg/mq bid given intermittently for 14 days within a 21-day cycle as a second-line therapy following a rapid progression on letrozole treatment given as a maintenance therapy. OUTCOMES: Our patient experienced a progression-free survival (PFS) >3 years with an exceptionally good quality of life (QoL). LESSONS: In ER+HER2- metastatic breast cancer patients, capecitabine monochemotherapy in second line may be associated with a particularly satisfactory PFS and no impact in terms of QoL. Future studies focused on biomarkers with predictive ability may help select patients who represent the best candidates to this treatment.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Capecitabina/uso terapêutico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Metástase Linfática/genética , Pessoa de Meia-Idade , Receptores Estrogênicos/genética
4.
Cochrane Database Syst Rev ; 9: CD004421, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31476253

RESUMO

BACKGROUND: Adjuvant chemotherapy improves survival in premenopausal and postmenopausal women with early breast cancer. Taxanes are highly active chemotherapy agents used in metastatic breast cancer. Review authors examined their role in early breast cancer. This review is an update of a Cochrane Review first published in 2007. OBJECTIVES: To assess the effects of taxane-containing adjuvant chemotherapy regimens for treatment of women with operable early breast cancer. SEARCH METHODS: For this review update, we searched the Specialised Register of the Cochrane Breast Cancer Group, MEDLINE, Embase, CENTRAL (2018, Issue 6), the WHO International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov on 16 July 2018, using key words such as 'early breast cancer' and 'taxanes'. We screened reference lists of other related literature reviews and articles, contacted trial authors, and applied no language restrictions. SELECTION CRITERIA: Randomised trials comparing taxane-containing regimens versus non-taxane-containing regimens in women with operable breast cancer were included. Studies of women receiving neoadjuvant chemotherapy were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias and quality of the evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and meta-analysis was performed using a fixed-effect model. The primary outcome measure was overall survival (OS); disease-free survival (DFS) was a secondary outcome measure. Toxicity was represented as odds ratios (ORs), and quality of life (QoL) data were extracted when present. MAIN RESULTS: This review included 29 studies (27 full-text publications and 2 abstracts or online theses). The updated analysis included 41,911 randomised women; the original review included 21,191 women. Taxane-containing regimens improved OS (HR 0.87, 95% confidence interval (CI) 0.83 to 0.92; high-certainty evidence; 27 studies; 39,180 women; 6501 deaths) and DFS (HR, 0.88, 95% CI 0.85 to 0.92; high-certainty evidence; 29 studies; 41,909 women; 10,271 reported events) compared to chemotherapy without a taxane. There was moderate to substantial heterogeneity across studies for OS and DFS (respectively).When a taxane-containing regimen was compared with the same regimen without a taxane, the beneficial effects of taxanes persisted for OS (HR 0.84, 95% CI 0.77 to 0.92; P < 0.001; 7 studies; 10,842 women) and for DFS (HR 0.84, 95% CI 0.78 to 0.90; P < 0.001; 7 studies; 10,842 women). When a taxane-containing regimen was compared with the same regimen with another drug or drugs that were substituted for the taxane, a beneficial effect was observed for OS and DFS with the taxane-containing regimen (OS: HR 0.80, 95% CI 0.74 to 0.86; P < 0.001; 13 studies; 16,196 women; DFS: HR 0.83, 95% CI 0.78 to 0.88; P < 0.001; 14 studies; 16,823 women). Preliminary subgroup analysis by lymph node status showed a survival benefit with taxane-containing regimens in studies of women with lymph node-positive disease only (HR 0.83, 95% CI 0.78 to 0.88; P < 0.001; 17 studies; 22,055 women) but less benefit in studies of women both with and without lymph node metastases or with no lymph node metastases. Taxane-containing regimens also improved DFS in women with lymph node-positive disease (HR 0.84, 95% CI 0.80 to 0.88; P < 0.001; 17 studies; 22,055 women), although the benefit was marginal in studies of women both with and without lymph node-positive disease (HR 0.95, 95% CI 0.88 to 1.02; 9 studies; 12,998 women) and was not apparent in studies of women with lymph node-negative disease (HR 0.99, 95% CI 0.86 to 1.14; 3 studies; 6856 women).Taxanes probably result in a small increase in risk of febrile neutropenia (odds ratio (OR) 1.55, 95% CI 0.96 to 2.49; moderate-certainty evidence; 24 studies; 33,763 women) and likely lead to a large increase in grade 3/4 neuropathy (OR 6.89, 95% CI 3.23 to 14.71; P < 0.001; moderate-certainty evidence; 22 studies; 31,033 women). Taxanes probably cause little or no difference in cardiotoxicity compared to regimens without a taxane (OR 0.87, 95% CI 0.56 to 1.33; moderate-certainty evidence; 23 studies; 32,894 women). Seven studies reported low-quality evidence for QoL; overall, taxanes may make little or no difference in QoL compared to chemotherapy without a taxane during the follow-up period; however, the duration of follow-up differed across studies. Only one study, which was conducted in Europe, provided cost-effectiveness data. AUTHORS' CONCLUSIONS: This review of studies supports the use of taxane-containing adjuvant chemotherapy regimens, with improvement in overall survival and disease-free survival for women with operable early breast cancer. This benefit persisted when analyses strictly compared a taxane-containing regimen versus the same regimen without a taxane or the same regimen with another drug that was substituted for the taxane. Preliminary evidence suggests that taxanes are more effective for women with lymph node-positive disease than for those with lymph node-negative disease. Considerable heterogeneity across studies probably reflects the varying efficacy of the chemotherapy backbones of the comparator regimens used in these studies. This review update reports results that are remarkably consistent with those of the original review, and it is highly unlikely that this review will be updated, as new trials are assessing treatments based on more detailed breast cancer biology.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Taxoides/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Gan To Kagaku Ryoho ; 46(9): 1405-1411, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530780

RESUMO

Abemaciclib, a selective cyclin dependent kinases 4 and 6(CDK4 & 6)inhibitor, is under development for the treatment of hormone receptor(HR)-positive, HER2-negative breast cancer. CDK4 & 6 inhibitors attenuate Rb phosphorylation resulting in a G1 arrest and tumor growth inhibition. Abemaciclib potently inhibits both CDK4 and CDK6, with 14-fold higher potency for CDK4-cyclin D1 complexes than CDK6-cyclin D3 in enzymatic assays. Low frequency of severe neutropenia requiring drug holiday in clinical trials of abemaciclib in breast cancer patients enables continuous daily dosing. Abemaciclib's preclinical difference in selectivity for CDK4 vs CDK6 could help explain its safety profile and ability to be dosed on a continuous schedule. Continuous inhibition of CDK4 & 6 by abemaciclib results in irreversible growth inhibition through induction of senescence and apoptosis in breast cancer cell lines. Abemaciclib shows its growth inhibitory effect particularly in estrogen receptor(ER)- positive breast cancer, and sensitivity to abemaciclib is associated with high ER levels and Rb positivity. In animals bearing ERpositive breast cancer, significant tumor growth inhibition was shown by single-agent and combination with anti-estrogen agents. Abemaciclib penetrates the blood-brain barrier and showed antitumor activity in glioma models. As described above, there are some characteristics demonstrate differences of abemaciclib and other CDK4 & 6 inhibitors. In clinical studies, abemaciclib has demonstrated efficacy and generally tolerable safety profile in HR-positive, HER2-negative breast cancer patients.


Assuntos
Aminopiridinas/uso terapêutico , Benzimidazóis/uso terapêutico , Neoplasias da Mama , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Neoplasias da Mama/tratamento farmacológico , Quinase 4 Dependente de Ciclina , Humanos
6.
Gan To Kagaku Ryoho ; 46(9): 1427-1431, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530783

RESUMO

AIM: We investigated the efficacy and safety of preoperative neoadjuvant chemotherapy(NAC)with a nanoparticle albumin- bound paclitaxel(nab-PTX)-containing regimen. PATIENTS AND METHODS: Twenty-eight female patients with Stage Ⅰ-Ⅲ breast cancer received nab-PTX(260mg/m / 2,q3w)±trastuzumab followed by FEC(5-fluorouracil 500 mg/m2 plus epiru- bicin 75 or 100mg/m / 2 plus cyclophosphamide 500 mg/m2: q3w)between June 2013 and January 2015. Patients with HER2- positive breast cancer received trastuzumab concurrently with nab-PTX. Clinical response, pathological complete response (pCR), and adverse events were evaluated. RESULTS: The overall pCR rate was 32%. The pCR rates for each subtype were as follows: HER2-type 86%, Luminal B-HER2 20%, triple-negative 17%, and Luminal B 0%. HER2-type breast cancer demon- strated the best response to this regimen. The clinical response rate for nab-PTX was 64%(18/28), and the safety profile was tolerable. CONCLUSION: nab-PTX±trastuzumab followed by FEC as NAC is effective and safe for operative breast cancer, especially HER2-type breast cancer.


Assuntos
Neoplasias da Mama , Nanopartículas , Terapia Neoadjuvante , Paclitaxel Ligado a Albumina , Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida , Epirubicina , Feminino , Humanos , Paclitaxel , Receptor ErbB-2
7.
Gan To Kagaku Ryoho ; 46(9): 1461-1463, 2019 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-31530791

RESUMO

We report 4 female patients with metastatic breast cancer who were administered TS-1 as a late-line treatment and showed favorable outcomes. Their average age was 66.3. The patients, all of whom had undergone prior treatment with both anthracyclines and taxanes, showed intrinsic Luminal A or B subtypes. After administration of TS-1 in the lines of 2 to 9 in metastatic settings, all patients showed a long progression-free survival with a favorable quality of life.


Assuntos
Neoplasias da Mama , Silicatos/uso terapêutico , Titânio/uso terapêutico , Idoso , Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Qualidade de Vida , Taxoides , Resultado do Tratamento
8.
Pharm Res ; 36(11): 154, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31482205

RESUMO

PURPOSE: Conjugation of nanocarriers with antibodies that bind to specific membrane receptors that are overexpressed in cancer cells enables targeted delivery. In the present study, we developed and synthesised two PAMAM dendrimer-trastuzumab conjugates that carried docetaxel or paclitaxel, specifically targeted to cells which overexpressed HER-2. METHODS: The 1H NMR, 13C NMR, FTIR and RP-HPLC were used to analyse the characteristics of the products and assess their purity. The toxicity of PAMAM-trastuzumab, PAMAM-doc-trastuzumab and PAMAM-ptx-trastuzumab conjugates was determined using MTT assay and compared with free trastuzumab, docetaxel and paclitaxel toward HER-2-positive (SKBR-3) and negative (MCF-7) human breast cancer cell lines. The cellular uptake and internal localisation were studied using flow cytometry and confocal microscopy, respectively. RESULTS: The PAMAM-drug-trastuzumab conjugates in particular showed extremely high toxicity toward the HER-2-positive SKBR-3 cells and very low toxicity towards to HER-2-negative MCF-7 cells. As expected, the HER-2-positive SKBR-3 cell line accumulated trastuzumab from both conjugates rapidly; but surprisingly, although a large amount of PAMAM-ptx-trastuzumab conjugate was observed in the HER-2-negative MCF-7 cells. Confocal microscopy confirmed the intracellular localisation of analysed compounds. The key result of fluorescent imaging was the identification of strong selective binding of the PAMAM-doc-trastuzumab conjugate with HER-2-positive SKBR-3 cells only. CONCLUSIONS: Our results confirm the high selectivity of PAMAM-doc-trastuzumab and PAMAM-ptx-trastuzumab conjugates for HER-2-positive cells, and demonstrate the utility of trastuzumab as a targeting agent. Therefore, the analysed conjugates present an promising approach for the improvement of efficacy of targeted delivery of anticancer drugs such as docetaxel or paclitaxel.


Assuntos
Antineoplásicos/química , Neoplasias da Mama/tratamento farmacológico , Dendrímeros/química , Docetaxel/química , Paclitaxel/química , Receptor ErbB-2/metabolismo , Trastuzumab/química , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Docetaxel/farmacologia , Interações de Medicamentos , Liberação Controlada de Fármacos , Corantes Fluorescentes/química , Humanos , Paclitaxel/farmacologia , Propriedades de Superfície , Trastuzumab/farmacologia , Resultado do Tratamento
9.
Medicine (Baltimore) ; 98(36): e16937, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490377

RESUMO

Metadherin (MTDH), also known as astrocyte elevated gene-1 (AEG-1), is an oncoprotein closely related to the development of breast cancer. However, few studies have been done on the expression and clinical significance of MTDH in human epidermal growth factor receptor-2 (HER-2) positive breast cancer patients.This study aimed to investigate the expression of MTDH in locally advanced HER-2 positive breast cancer, and evaluate the clinical significance of MTDH in predicting the prognosis of patients with HER-2 positive advanced breast cancer who received the neoadjuvant chemotherapy plus trastuzumab.In 144 HER-2 positive breast cancer tissues, 79 cases showed high expression of MTDH and 65 cases showed low expression. The expression of MTDH in locally advanced HER-2 positive breast cancer tissues was correlated with TNM stage, lymph node metastasis, Miller-Payne (MP) grade, and pathologic complete response (pCR) status (P < .05), but was not correlated with patient age, estrogen receptor (ER) expression level, progesterone receptor (PR) expression level, and Ki-67 expression level (P > .05). Kaplan-Meier univariate analysis revealed a negative correlation between MTDH expression and the disease-free survival (DFS) and overall survival (OS) in the post-operative patients with locally advanced HER-2 positive breast cancer (log rank test: P < .001). By using the COX proportional hazard regression model, it was found that MTDH expression, TNM stage, lymph node metastasis, and Ki-67 expression were closely related to DFS in patients. The hazard ratio (HR) of high MTDH expression was 1.816 (95% CI: 1.165-2.829). In addition, MTDH expression, TNM stage, and lymph node metastasis were also closely related to the OS of patient. The HR of the high expression of MTDH was 2.512 (95% CI: 1.472-4.286). The expression of MTDH in tumor tissues of patients with HER2-positive locally advanced breast cancer was significantly elevated, which was related to the poor pathological features.High MTDH expression was closely correlated with poor prognosis of patients and was an important factor affecting tumor progression.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Moléculas de Adesão Celular/biossíntese , Receptor ErbB-2/biossíntese , Trastuzumab/uso terapêutico , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Receptores Estrogênicos/biossíntese , Receptores de Progesterona/biossíntese
10.
Medicine (Baltimore) ; 98(36): e17009, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490383

RESUMO

Erythrina corallodendron L., a kind of landscape tree, has long been used as a traditional medicine. In this study, the composition of essential oil extracted from the leaves was analysed by GC-MS (gas chromatograph-mass spectrometer), with linalool identified as the main compound. Its cytotoxicity against MDA-MB-231, MCF-7 and HMLE cells was examined by MTT and cloning assays. Transwell and wound-healing assays were used to examine the inhibition of migration and invasion. Western blot, qRT-PCR and immunofluorescence staining were used to measure the mRNA and protein expression of factors related to EMT (snail, slug, E-cadherin, N-cadherin and vimentin). The essential oil of Erythrina corallodendron leaves was found to inhibit the proliferation, migration and invasion of breast cancer cells in a dose-dependent manner. The findings of this study suggest that the essential oil of E. corallodendron leaves may merit further investigation as a potential clinical or adjuvant drug for treating breast cancer migration and invasion.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Fitogênicos/análise , Neoplasias da Mama/tratamento farmacológico , Erythrina/química , Óleos Voláteis/uso terapêutico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Células MCF-7 , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Fitoterapia , Folhas de Planta/química
11.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(3): 296-302, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31496162

RESUMO

OBJECTIVE: To investigate the effects of high dose vitamin C (VC) on proliferation of breast cancer cells and to explore its mechanisms. METHODS: Human breast cancer cells Bcap37 and MDA-MB-453 were treated with VC at low dose (0.01 mmol/L), medium dose (0.10 mmol/L) and high dose (2.00 mmol/L). Cell proliferation was determined with CCK-8 assay, protein expression was evaluated by Western blot, and the secretion of lactic acid in tumor cells was detected by colorimetric method. Bcap37 cells were inoculated in nude mice, and tumor baring nude mice were intraperitoneally injected with high VC(4 g/kg, VC group, n=5)or normal saline (control group, n=5) for 24 d. Tumor weight and body weight were calculated. RESULTS: In vitro experiments demonstrated that high dose VC significantly inhibited cell proliferation in Bcap37 and MDA-MB-453 cells (all P<0.01); the expressions of Glut1 and mTOR signaling pathway-related proteins were decreased (all P<0.05); and the secretion of lactic acid was also markedly reduced (all P<0.05). In vivo experiment showed that the tumor weight was decreased in mice treated with high-dose VC as compared with control group (P<0.05), but no difference in body weights between two groups was observed. CONCLUSIONS: High dose VC may inhibit proliferation of breast cancer cells both in vitro and in vivo through reducing glycolysis and protein synthesis.


Assuntos
Ácido Ascórbico , Neoplasias da Mama , Glicólise , Biossíntese de Proteínas , Animais , Ácido Ascórbico/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Biossíntese de Proteínas/efeitos dos fármacos
12.
Medicine (Baltimore) ; 98(37): e17114, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517847

RESUMO

BACKGROUND: We will investigate the efficacy and safety of weekly cisplatin (WC) for treatment of patients with breast cancer (BC) systematically. METHODS: This study will describe and critically appraise shared decision approaches used in randomized controlled trials of WC for treatment of patients with BC. We will comprehensively search the following databases: PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, PsycINFO, Allied and Complementary Medicine Database, Wanfang, and Chinese Biomedical Literature Database from inception through July 1, 2019. We will utilize RevMan V.5.3 software (London, UK) for statistical analysis. RESULTS: This study will systematically explore the efficacy and safety of WC for the treatment of patients with BC through evaluating primary outcomes of overall survival, pathological complete response; and secondary outcomes of cancer-specific survival, recurrence-free survival, disease-free survival, quality of life, and toxicities. CONCLUSION: This study will provide latest evidence of WC for the treatment of patients with BC. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019145358.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cisplatino/normas , Adulto , Cisplatino/uso terapêutico , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Resultado do Tratamento
14.
Pol J Pathol ; 70(2): 91-99, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556559

RESUMO

Currently, breast cancer chemotherapy response can be predicted based on various parameters, with common reporting of tumour grade and Ki67 proliferation index. We analysed their association with pathological complete response (pCR) in a multivariate approach. The study was carried out in a group of 353 patients, treated by preoperative chemotherapy and prospectively observed. In selected patients, parallel to routing core needle biopsy assessment, gene expression profile of tumour was analysed by oligonucleotide microarrays. Tumour parameters associated with pCR in univariate analysis were: tumour grade, nuclear grade, mitotic index, Ki67, oestrogen and progesterone receptor (all p < 0.0001), and triple-negative status (p = 0.0032). The highest increase of pCR chance was observed in patients with high-grade tumours and with Ki67 ≥ 20%. In multivariate analysis, only tumour grade and oestrogen receptor status were predictive for pCR independently of other variables, with high grade increasing the odds of pCR 2.42 fold, and high ER decreasing the chance of pCR 0.41 fold. Tumour grading reflects important biological features of breast cancer and is not inferior to proliferation markers, including Ki67. It should be taken into account in decision-making for preoperative chemotherapy in parallel to breast cancer biologic subtypes, because grade 3 tumours exhibit a higher proportion of pCR.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Gradação de Tumores , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/cirurgia , Feminino , Humanos , Antígeno Ki-67/metabolismo , Estudos Prospectivos , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Resultado do Tratamento
15.
Chem Commun (Camb) ; 55(72): 10792-10795, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31432816

RESUMO

Hypoxia, as an important feature in tumor sites, greatly hinders the performance of photosensitizers, thus affecting the efficacy of photodynamic therapy (PDT). Therefore, designing and preparing new photosensitizer with high photosensitivity under hypoxic condition presents a great challenge that urgently needs to be solved. In this work, a new nano-MOF material using Mn(ii) as the active center can catalytically decompose high concentrations of H2O2 in tumor cells to generate O2, thereby improving the PDT efficacy in hypoxic tumors. The Mn-MOF also produces 1O2 under light irradiation, which finally induces cancer cell apoptosis. This work offers a new strategy for the design and discovery of effective photosensitizers for PDT.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Manganês/farmacologia , Estruturas Metalorgânicas/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Peróxido de Hidrogênio/metabolismo , Manganês/química , Estruturas Metalorgânicas/química , Camundongos , Oxigênio/metabolismo , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Propriedades de Superfície
16.
Medicine (Baltimore) ; 98(32): e16770, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393399

RESUMO

BACKGROUND: Osteoporosis is a major side effect of aromatase inhibitors (AIs), which are greatly effective in the treatment of breast cancer. However, there are no satisfactory measures against osteoporosis. In this multicenter, randomized, comparative study, we evaluate the efficacy of denosumab for preventing loss of bone mineral density (BMD) induced by adjuvant therapy with AI s in breast cancer patients with normal BMD. PATIENTS AND METHODS: The bone loss-suppressing effect of denosumab will be comparatively evaluated in postmenopausal patients scheduled to receive letrozole or anastrozole as a postoperative endocrine therapy for stage I-IIIA hormone-sensitive breast cancer and a control group. Patients will be administered letrozole 2.5 mg or anastrozole 1 mg once a day, and the treatment will be continued for 5 years unless recurrence, secondary cancer, or unacceptable toxicity develops. Patients in the denosumab group will receive a subcutaneous injection of 60 mg of denosumab every 6 months. The primary endpoint is the rate of change in the lumbar spine (L1-L4) BMD, as determined by dual-energy X-ray absorptiometry (DXA), 12 months after the start of the injection. The secondary endpoints were ETHICS AND DISSEMINATION:: The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating faculties. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT03324932, Japan Registry of Clinical Trial (jRCT): CRB5180001.


Assuntos
Inibidores da Aromatase/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Denosumab/administração & dosagem , Osteoporose/induzido quimicamente , Osteoporose/prevenção & controle , Adulto , Inibidores da Aromatase/uso terapêutico , Biomarcadores , Osso e Ossos/metabolismo , Neoplasias da Mama/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos de Pesquisa
17.
Life Sci ; 234: 116783, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31442552

RESUMO

Breast cancer (BCa) is the most commonly diagnosed lethal cancer in women worldwide. Notch signaling pathway is directly linked to BCa recurrence and aggressiveness. Natural remedies are becoming a prime choice to overcome against cancer due to lesser side effect and cost-effectiveness. Bulbine frutescens (Asphodelaceae), a traditional medicinal plant in South Africa possess bioactive flavonoids and terpenoids. Polar (methanol) and non-polar (hexane) B. frutescens plant extracts were prepared. GC-MS analysis revealed the differential presence of secondary metabolites in both methanolic and hexane extracts. We hereby first time evaluated the anticancer potential of B. frutescens methanolic and hexane extract in triple-negative and luminal BCa cells. B. frutescens extracts significantly decreased cell viability (IC50 4.8-28.4 µg/ml) and induced cell cycle arrest at G1 phase in MDA-MB-231 and T47D cells as confirmed by spectrophotometry and flow cytometry technique. RT-PCR analysis of cell cycle (cyclin D1, CDK4, and p21) and apoptosis modulating genes (caspase 3, Bcl2 and survivin) revealed upexpression of p21, and caspase 3, and down expression of cyclin D1, CDK4, Bcl2 and survivin genes in extract-treated BCa cells. Fluorescence spectrophotometry and confocal microscopy showed B. frutescens induced nuclear morphology and mitochondrial integrity disruption, and increased reactive oxygen species production in MDA-MB-231 and T47D cells. Flow cytometric apoptosis analysis of B. frutescens extracts treated MDA-MB-231 cells showed ≈13% increase in early apoptotic population in comparison to non-treated cells. Dual-Luciferase Reporter assay confirmed notch promoter inhibitory activity of B. frutescens extracts. Moreover, RTPCR analysis showed down regulation of notch responsive genes (Hes1 and Hey1) at transcription levels in extract-treated BCa cells. Western Blot analysis showed increased procaspase 3 protein expression in extract-treated BCa cells. In all the assays methanolic extract showed better anti-cancer properties. Literature-based identification of methanol soluble phytochemicals in B. frutescens and in silico docking study revealed Bulbineloneside D as a potent ϒ-secretase enzyme inhibitor. In comparison to standard notch inhibitor, lead phytochemical showed two additional hydrophobic interactions with Ala80 and Leu81 amino acids. In conclusion, B. frutescens phytochemicals have cell cycle arrest, ROS production, apoptosis induction, and mitochondria membrane potential disruption efficacy in breast cancer cells. B. frutescens phytochemicals have the ability to downregulate the notch signaling pathway in triple-negative and luminal breast cancer cells.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Xanthorrhoeaceae/química , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
18.
Adv Exp Med Biol ; 1152: 217-228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456185

RESUMO

Trastuzumab represents the predominant therapy to target breast cancer subtype marked by HER2 amplification. It has been in use for two decades and its continued importance is underlined by recent FDA approvals of its biosimilar and conjugated versions. Progression to an aggressive disease with acquisition of resistance to trastuzumab remains a major clinical concern. In addition to a number of cellular signaling pathways being investigated, focus in recent years has also shifted to epigenetic and non-coding RNA basis of acquired resistance against trastuzumab. This article provides a succinct discussion on the most recent advances in our understanding of such factors.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Receptor ErbB-2/genética , Trastuzumab/uso terapêutico , Anticorpos Monoclonais Humanizados , Feminino , Humanos
19.
Adv Exp Med Biol ; 1152: 229-241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456186

RESUMO

A large proportion of breast cancer patients are estrogen receptor positive. They generally benefit from tamoxifen, the drug that targets estrogen receptor signaling. However, de novo and acquired resistance against tamoxifen is well known. A number of signaling pathways and de-regulated factors have been evaluated to better understand the mechanism(s) of tamoxifen resistance. For past several years, non-coding RNAs have also gained attention as the putative regulators and determinants of tamoxifen resistance. A number of reports have documented evidence from in vitro and/or in vivo studies, as well as from evaluation of clinical samples, to showcase the power of non-coding RNAs as mediators of tamoxifen resistance and the predictors of disease relapse. This article puts into perspective the available information on microRNAs and the long non-coding RNAs regarding their ability to tweak resistance vs. sensitivity to tamoxifen.


Assuntos
Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Tamoxifeno/farmacologia , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos
20.
Adv Exp Med Biol ; 1152: 243-252, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456187

RESUMO

Sequencing technologies have allowed us to characterize highly heterogeneous molecular landscape of breast cancer with unprecedented details. Tremendous breakthroughs have been made in unraveling contributory role of signaling pathways in breast cancer development and progression. It is becoming progressively more understandable that deregulation of spatio-temporally controlled pathways underlie development of resistance against different drugs. TRAIL mediated signaling has attracted considerable appreciation because of its characteristically unique ability to target cancer cells while leaving normal cells intact. Discovery of TRAIL was considered as a paradigm shift in molecular oncology because of its conspicuous ability to selectively target cancer cells. There was an exponential growth in the number of high-quality reports which highlighted cancer targeting ability of TRAIL and scientists worked on the development of TRAIL-based therapeutics and death receptor targeting agonistic antibodies to treat cancer. However, later studies challenged simplistic view related to tumor targeting ability of TRAIL. Detailed mechanistic insights revealed that overexpression of anti-apoptotic proteins, inactivation of pro-apoptotic proteins and downregulation of death receptors were instrumental in impairing apoptosis in cancer cells. Therefore researchers started to give attention to identification of methodologies and strategies to overcome the stumbling blocks associated with TRAIL-based therapeutics. Subsequent studies gave us a clear picture of signaling cascade of TRAIL and how deregulation of different proteins abrogated apoptosis. In this chapter we have attempted to provide an overview of the TRAIL induced signaling, list of proteins frequently deregulated and modern approaches to strategically restore apoptosis in TRAIL-resistant breast cancers.


Assuntos
Apoptose , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos , Transdução de Sinais , Ligante Indutor de Apoptose Relacionado a TNF/genética , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Feminino , Humanos
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