Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 54.417
Filtrar
1.
Lancet ; 395(10226): 817-827, 2020 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-32145796

RESUMEN

The development and approval of cyclin-dependent kinase (CDK) 4 and 6 inhibitors for hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer represents a major milestone in cancer therapeutics. Three different oral CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, have significantly improved progression-free survival by a number of months when combined with endocrine therapy. More recently, improvement in overall survival has been reported with ribociclib and abemaciclib. The toxicity profile of all three drugs is well described and generally easily manageable with dose reductions when indicated. More myelotoxicity is observed with palbociclib and ribociclib, but more gastrointestinal toxicity is observed with abemaciclib. Emerging data is shedding light on the resistance mechanisms associated with CDK4/6 inhibitors, including cell cycle alterations and activation of upstream tyrosine kinase receptors. A number of clinical trials are exploring several important questions regarding treatment sequencing, combinatorial strategies, and the use of CDK4/6 inhibitors in the adjuvant and neoadjuvant settings, thereby further expanding and refining the clinical application of CDK4/6 inhibitors for patients with breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Inhibidores de Proteínas Quinasas/uso terapéutico , Ciclo Celular/efectos de los fármacos , Ensayos Clínicos como Asunto , Femenino , Predicción , Humanos , Receptores Estrogénicos , Receptores de Progesterona
2.
Medicine (Baltimore) ; 99(11): e19566, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176115

RESUMEN

Chemotherapy may cause ovarian toxicity and infertility. Cancer patients are usually overwhelmed, and focus exclusively on cancer diagnosis and may not pay attention to fertility-related issues. In this paper we look at the rate of amenorrhea and fertility counseling among such young patients.Premenopausal women with early-stage breast cancer treated with adjuvant or neoadjuvant chemotherapy were recruited. Amenorrhea was defined as absence of menstruation for ≥12 months after the completion of chemotherapy.A total of 94 patients met the eligibility criteria and were included in this analysis. Median age at diagnosis was 35.7 (range, 22-44) years. Seventy-nine (85.9%) respondents were counseled about amenorrhea and 37 (40.2%) were considering having children. Long-term amenorrhea was reported by 51 (54.3%) patients. The addition of taxanes to anthracyclines, in 2 different regimens, increased the risk of amenorrhea to 69.2% and 66.7% compared to 38.9% with anthracycline-alone, P < .0001. Longer duration of chemotherapy (≥24 weeks) might also be associated with higher rate of amenorrhea (67.7%) compared to 43.4% in those who had shorter duration (<24 weeks), P = .031.The addition of taxanes to anthracycline-based chemotherapy increased the risk of amenorrhea. However, shorter duration of chemotherapy, even with taxanes, may lower such risk. Our study highlights the importance of fertility counseling to improve fertility preservation rates. Given the importance of taxanes, shorter regimens are associated with lower amenorrhea rates and should be preferred over longer ones.


Asunto(s)
Amenorrea/inducido químicamente , Antraciclinas/efectos adversos , Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Preservación de la Fertilidad , Taxoides/efectos adversos , Adulto , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/efectos adversos , Consejo , Femenino , Humanos , Jordania , Estadificación de Neoplasias , Estudios Retrospectivos , Adulto Joven
3.
Bull Cancer ; 107(2): 148-156, 2020 Feb.
Artículo en Francés | MEDLINE | ID: mdl-32057466

RESUMEN

Over the past years, planet oncology has kept changing and moving forward. Recent results of important clinical trials are challenging our daily practices. With modesty, the Editorial Board of BulletinduCancer has selected some clinical trials they consider as "must-know about" even if they go beyond our medical fields.


Asunto(s)
Ensayos Clínicos como Asunto , Neoplasias/terapia , Aminopiridinas/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias del Sistema Digestivo/terapia , Femenino , Neoplasias de los Genitales Femeninos/terapia , Humanos , Neoplasias Pulmonares/terapia , Masculino , Terapia Molecular Dirigida , Neoplasias Primarias Desconocidas/terapia , Neoplasias de la Próstata/terapia , Purinas/uso terapéutico
4.
J Photochem Photobiol B ; 204: 111808, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32006892

RESUMEN

Photodynamic therapy (PDT) is effective in the treatment of different types of cancer, such as basal cell carcinoma and other superficial cancers. However, improvements in photosensitizer delivery are still needed, and the use of PDT against more deeply located tumors has been the subject of many studies. Thus, the goal of this study was to evaluate the efficacy of a nanoemulsion containing aluminium-phthalocyanine (AlPc-NE) as a mediator of photodynamic therapy (PDT-AlPc-NE) against grafted 4T1 breast adenocarcinoma tumors in mice (BALB/c). Short after the appearance of the tumor, the animals were divided into groups (n = 5) as follows: untreated; only AlPc-NE and treated with PDT-AlPc-NE. The tumor volume was measured with a digital calliper at specific times. The presence of metastasis in the lungs was evaluated by microtomography and histopathological analyses. The results show that the application of PDT-AlPc-NE eradicated the transplanted tumors in all the treated animals, while the animals from control groups presented a robust increase in the tumor volume. Still more significantly, microtomography showed the animals submitted the PDT-AlPc-NE to be free of detectable metastasis in the lungs. The histological analysis of the lungs further confirmed the results verified by the microtomography. Therefore, this study suggests that PDT-AlPc-NE is effective in the elimination of experimentally grafted breast tumors in mice and also in preventing the formation of metastasis in the lungs.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Aluminio/química , Neoplasias de la Mama/tratamiento farmacológico , Indoles/química , Neoplasias Pulmonares/tratamiento farmacológico , Nanoestructuras/química , Fármacos Fotosensibilizantes/uso terapéutico , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Animales , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Ratones , Ratones Endogámicos BALB C , Nanoestructuras/uso terapéutico , Nanoestructuras/toxicidad , Fotoquimioterapia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Trasplante Homólogo , Microtomografía por Rayos X
5.
J Photochem Photobiol B ; 204: 111811, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32028187

RESUMEN

The development of multidrug resistance is often associated with the over-expression of P-glycoprotein (P-gp). This protein prevents drug accumulation and extrudes them out of the cell before they reach the intended target. The aim of this study was to develop an in vitro MCF-7 cell line with increased expression of P-gp and test the phototoxicity of a novel photoactivated zinc phthalocyanine tetrasulfonic acid (ZnPcS4) on these cells. The over-expressed P-gp MCF-7 cells (MCF-7/DOX) were developed from wildtype (WT) MCF-7 cells by a stepwise continuous exposure of the WT cells to different concentrations of Doxorubicin (DOX) (0.1 - 1 µM) over a period of 4 months. The P-gp expression was measured using flow cytometry, immunofluorescence and enzyme immunoassay. To verify whether zinc phthalocyanine-mediated photodynamic therapy (ZnPcS4 - PDT) is effective in MCF-7/DOX, we studied the subcellular localization, phototoxicity and nuclear damage. The flow cytometry result showed two distinct peaks of P-gp positive and negative expression in MCF-7/DOX cell population, which correlates with the ELISA-based assay (p˂0.001). The ME16C (Normal breast cells) was used as control. The localization studies showed that ZnPcS4 have greater affinity for lysosome than mitochondria. Phototoxicity results indicated that photoactivated zinc phthalocyanine decreased the cell proliferation and viability as the drug and laser light dosages increased to 16 µM and 20 J/cm2 respectively. PDT-induced cytotoxicity using lactose dehydrogenase (LDH) enzyme leakage as measure did not increase likewise. The ZnPcS4-induced PDT was less effective for MCF-7/DOX cells which could be attributed to decreased retention of ZnPcS4 in major cellular organelles due to the presence of increased drug efflux P-gp. The current findings suggest that, increased P-gp expression, a characteristic of multidrug resistance together with other related intrinsic mechanisms might contribute to render MCF-7/DOX cells less sensitive to ZnPcS4-induced phototoxicity.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Proliferación Celular/efectos de los fármacos , Indoles/farmacología , Láseres de Semiconductores , Compuestos Organometálicos/farmacología , Adenosina Trifosfato/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Doxorrubicina/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de la radiación , Femenino , Humanos , Indoles/química , Células MCF-7 , Compuestos Organometálicos/química , Fotoquimioterapia , Rodamina 123/química , Rodamina 123/metabolismo
6.
Anticancer Res ; 40(2): 837-840, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014926

RESUMEN

BACKGROUND/AIM: The study aimed to test the potential for increasing the antiproliferative activity of 5-fluorouracil against breast cancer cells of various molecular subtypes by vitamin D receptor (VDR) agonists, calcitriol and tacalcitol, used at a low concentration of 10 nM. MATERIALS AND METHODS: Calcitriol and tacalcitol were used to increase the antiproliferative effect of 5-fluorouracil against the following human breast cancer cell lines: MCF-7, T47D, BT-474 (luminal); JIMT-1, SKBR-3 (HER2-enriched); MDA-MB-231 (triple-negative/basal-B), and non-malignant MCF-10A breast epithelial cells. RESULTS: Both calcitriol and tacalcitol significantly increased the sensitivity of MCF-7 and BT-474 cells to the antiproliferative effect of 5-fluorouracil, while no increase in the sensitivity of MDA-MB-231 cells to 5-fluorouracil treatment was observed. CONCLUSION: The VDR agonist used at the relatively low concentration of 10 nM may increase the sensitivity of breast cancer cells, at least of the luminal subtype, to the antiproliferative effect of 5-fluorouracil.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Fluorouracilo/uso terapéutico , Receptores de Calcitriol/agonistas , Línea Celular Tumoral , Fluorouracilo/farmacología , Humanos , Células MCF-7/metabolismo
7.
Anticancer Res ; 40(2): 857-864, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32014929

RESUMEN

AIM: The purpose of this study was to determine the level of adherence to adjuvant aromatase inhibitor (AI) therapy and factors associated with non-adherence among Hispanic/Latino women with hormonal receptor-positive breast cancer (BC) treated at an academic center at the American-Mexican border city of El Paso, TX. PATIENTS AND METHODS: Institutional Review Board approval was obtained in this cross-sectional study using the validated Morisky Medication Adherence Scale to assess patient adherence to AI therapy. Patients diagnosed with stage I-III hormonal receptor-positive, human epidermal growth factor receptor 2-negative BC who were on adjuvant AIs therapy were recruited from the Texas Tech University Health Sciences Center El Paso breast clinic. RESULTS: Between September 2017 and August 2018, 122 consecutive patients were enrolled; 119 were analyzed, three were lost to follow up. The mean age was 61.6±9.4 years, and 109 (91.6%) self-identified as Hispanic/Latino. A total of 58% reported an annual income of $15,000 or less. Overall, 40.3% had completed eighth grade or less education, 31.9% high school, and 12% had obtained a technical degree. The majority of patients (56%) had either a medium (45%) or a low level of adherence (11%). High adherence was noted in 44% of participants. Seven (5.6%) patients scored 2 or below on a 4-point scale for intentional adherence, and 18 (13.5%) scored 2 or below on a 4-point scale for unintentional adherence. CONCLUSION: These data suggest that the majority of Hispanic/Latino women with breast cancer have medium or low levels of adherence to therapy with AIs. Factors associated with medium and low adherence were unintentional (forgetfulness), but also included intentional factors, such as avoidance of adverse effects and delays with obtaining refills (cost-related nonadherence).


Asunto(s)
Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Inhibidores de la Aromatasa/farmacología , Estudios Transversales , Femenino , Hispanoamericanos , Humanos , Persona de Mediana Edad , Posmenopausia , Estudios Prospectivos , Encuestas y Cuestionarios
8.
Medicine (Baltimore) ; 99(8): e19083, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080081

RESUMEN

BACKGROUND: Breast cancer is the most prevalent cancer in females and disease recurrence remains a significant problem. To prevent recurrence, tamoxifen is prescribed for at least 5 years. However, among patients who receive tamoxifen, individual responses are highly variable. These responses are affected by the type, frequency, and severity of endocrine symptoms, as well as adherence rates. Polymorphisms in genes involved in the metabolism of tamoxifen (ie, CYP3A4, CYP2D6) may influence responses to tamoxifen. In this study, the inter-relationships among endocrine symptoms, drug adherence, and genetic polymorphisms in Chinese breast cancer patients receiving tamoxifen therapy will be examined. We hypothesize that patients with more severe endocrine symptoms will be less likely to adhere to tamoxifen treatment. In addition, we hypothesize that a relationship will exist between the severity of tamoxifen-induced symptoms and allelic variations in tamoxifen metabolism-related genes. Although many association studies have determined that select genotypes influence the efficacy of tamoxifen, very few studies have investigated for associations between tamoxifen-induced endocrine symptoms and these polymorphisms. OBJECTIVES: The aim of this study was to characterize genetic polymorphisms in tamoxifen metabolism-associated genes in Chinese women with breast cancer and to explore the inter-relationships between genetic polymorphisms, endocrine symptoms, and adherence to tamoxifen. METHOD: We will conduct a prospective cohort study that follows 200 Chinese women over 18 months and assess treatment-related symptoms and genetic variations. Endocrine symptoms and drug adherence will be determined through interview-administered standardized questionnaires. Polymorphisms in drug metabolism genes will be determined using real-time polymerase chain reaction based genotyping method. Data will be analyzed to determine associations between allelic variations, endocrine symptoms, and adherence. DISCUSSION: The proposed study will evaluate for polymorphisms in gene(s) that are associated with tamoxifen-related endocrine symptoms and adherence with tamoxifen. We will explore the relationships between genotypes, endocrine symptoms, and drug adherence in Chinese breast cancer patients. Findings from this study may assist clinicians to identify patients at higher risk for a worse symptom experience and lower adherence rates and enable them to initiate appropriate interventions. In the long term, the findings from this study may be used to develop and test tailored symptom management interventions for these patients.


Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Enfermedades del Sistema Endocrino/inducido químicamente , Tamoxifeno/efectos adversos , Alelos , Antineoplásicos Hormonales/metabolismo , Antineoplásicos Hormonales/uso terapéutico , Grupo de Ascendencia Continental Asiática/genética , Neoplasias de la Mama/epidemiología , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP3A/genética , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Cooperación del Paciente , Polimorfismo de Nucleótido Simple , Prevalencia , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Tamoxifeno/metabolismo , Tamoxifeno/uso terapéutico
9.
Life Sci ; 248: 117454, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32088211

RESUMEN

AIMS: Dihydroartemisinin (DHA) is currently considered as the promising cancer therapeutic drug. In this study, we aimed to investigate the anti-proliferative and anti-metastasis effects of DHA. MAIN METHODS: Utilizing breast cancer cells MCF-7, MDA-MB-231 and BT549, cell proliferation, migration and invasion were detected. RT-qPCR was performed to detect CIZ1, TGF-ß1 and Snail expression, and the interactions of these related molecules were analyzed by GeneMANIA database. Western blot detected CIZ1, TGF-ß1/Smads signaling and Snail expression in DHA-treated cells, in TGFß1-induced cells with enhanced metastatic capacity, and in cells treated with DHA plus TGFß1/TGFß1 inhibitor SD-208. KEY FINDINGS: Results indicated DHA inhibited breast cancer cell proliferation and migration, with more potent effects compared with that of artemisinin. RT-qPCR and Western blot showed DHA inhibited CIZ1, TGF-ß1 and Snail expression, and these molecules were shown to have protein-protein interactions by bioinformatics. Furthermore, TGFß1-treatment enhanced MCF-7 migration and invasion, and CIZ1, TGF-ß1/Smads signaling and snail activities; DHA, SD-208, combination of DHA and SD-208 reversed these conditions, preliminarily proving the cascade regulation between TGF-ß1 signaling and CIZ1. MCF-7 xenografts model demonstrated the inhibition of DHA on tumor burden, and its mechanisms and well-tolerance in vivo; combination of DHA and SD-208 tried by us for the first time showed better treatment effects, but possible liver impairment made its use still keep cautious. SIGNIFICANCE: DHA treatment inhibits the proliferation and metastasis of breast cancer, through suppressing TGF-ß1/Smad signaling and CIZ1, suggesting the promising potential of DHA as a well-tolerated antitumor TGF-ß1 pathway inhibitor.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Artemisininas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica , Proteínas Nucleares/genética , Factor de Crecimiento Transformador beta1/genética , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Transición Epitelial-Mesenquimal , Femenino , Humanos , Metástasis Linfática , Células MCF-7 , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/metabolismo , Pteridinas/farmacología , Transducción de Señal , Proteínas Smad/genética , Proteínas Smad/metabolismo , Factores de Transcripción de la Familia Snail/antagonistas & inhibidores , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
10.
Life Sci ; 248: 117463, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32097663

RESUMEN

Breast cancer is one of the well-known malignant tumors among women. In spite of attempts to classifying breast cancer according to its histological and molecular properties, it is almost considered as a dilemma in treatment. Nowadays, public and medical attentions have primary focused on foods with anti-cancer properties to alleviate the cancer problems. Flavonoid components such as Quercetin (Qu) as dietary substances with high attention of ordinary people might provide potential of alternative or complementary medicine in breast cancer. With regard to the wide range of health benefits of Qu, researchers have been generally convinced to bring Qu as natural compounds in cancer therapy. Moreover, the high cost of standard cancer treatments and the failure of most conventional treatments have led the medical community to pursue cost-effective prevention and treatment. As a result, a great deal of concentration is attracted to diet/cancer reciprocal action. Therefore, this review study has aimed to identify what has revealed the critical properties of Qu such as anti-inflammatory, anti-oxidant, and even its effect on proliferation, angiogenesis, or apoptosis that are considered as anti-tumor property to enhance breast cancer treatment.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Antioxidantes/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica , Neovascularización Patológica/tratamiento farmacológico , Quercetina/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos Clínicos como Asunto , Femenino , Humanos , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Life Sci ; 248: 117469, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32109485

RESUMEN

AIMS: Histone deacetylases inhibitors have shown favorable antitumor activity in clinical investigations. In the present study, we assessed the effects of a novel hydroxamic acid-based HDAC inhibitor, SB939, on breast cancer metastasis and tumor growth and characterized the underlying molecular mechanisms. MAIN METHODS: MTS, Wound-healing, and Transwell chamber invasion assays were used to detect the inhibition effects of SB939 on proliferation, migration, and invasion of breast cancer cells. Western blot, cellular immunofluorescence, and EMSA were used to explore the molecular mechanism of SB939 in suppressing breast cancer metastasis. MDA-MB-231 subcutaneous tumor-bearing model of nude mice and the spontaneous metastasis model of breast cancer were both applied to verify in vivo anti-tumor growth and anti-metastatic effects. KEY FINDINGS: Our results demonstrated that SB939 at 0.5-1 µmol/L markedly impaired the chemotactic motility of breast cancer cells. SB939 reversed epithelial-mesenchymal transition (EMT) process, as evidenced by upregulation E-cadherin expression and downregulation expressions of N-cadherin and vimentin through increasing the levels of ac-histone H3 and H4 and drecreasing the expressiongs of HDAC 5 and 4. This cascade inhibition mediated by SB939 was well interpreted by inactivating phosphorylation of STAT3, blocking its DNA-binding activity, and decreasing the expressions of STAT3-dependent target genes, including MMP2 and MMP9. Furhtermore, we found that SB939 significantly inhibited breast cancer metastasis and tumor growth in vivo and showed superior anti-tumor properties compared with SAHA in two breast cancer animal models. SIGNIFICANCE: Our findings indicate that SB939 may be an effective therapeutic option for treating advanced breast cancer.


Asunto(s)
Antineoplásicos/farmacología , Bencimidazoles/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica , Inhibidores de Histona Desacetilasas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Femenino , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Histonas/genética , Histonas/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones , Ratones Desnudos , Proteínas Represoras/antagonistas & inhibidores , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Carga Tumoral/efectos de los fármacos , Vimentina/genética , Vimentina/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Crit Rev Oncol Hematol ; 147: 102886, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32014673

RESUMEN

In several tumors the PI3K/AKT/mTOR pathway is frequently disrupted, an event that results in uncontrolled cell proliferation and tumor growth. Through the years, several compounds have been developed to inhibit the pathway at different steps: the mammalian target of rapamycin (mTOR) seemed to be the most qualified target. However, this kinase has such a key role in cell survival that mechanisms of resistance are rapidly developed. Nevertheless, clinical results obtained with mTOR inhibitors in breast cancer, renal cell carcinoma, neuroendocrine tumors and mantle cell lymphoma push oncologists to actively further develop these drugs, maybe by better selecting the population to which they are offered, through the research of predictive factors of responsiveness. In this review, we aim to describe mechanisms of resistance to mTOR inhibitors, from preclinical and clinical perspectives.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Linfoma de Células del Manto , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Adulto , Proliferación Celular , Resistencia a Antineoplásicos , Humanos , Inhibidores de Proteínas Quinasas
13.
Medicine (Baltimore) ; 99(3): e18812, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32011488

RESUMEN

RATIONALE: Breast cancer is the most commonly diagnosed malignancies in females. The most common sites of metastasis are bone, lung, liver, and brain. Gastrointestinal and adrenal gland metastasis from breast cancer are rare. Simultaneous metastases are extremely rare. Therefore, it is critically important to choose proper examination and treatment since the rapid diagnosis and primary treatment can significantly affect the survival of patients. To the best of our knowledge, this was the first case of initial dual metastasis. PATIENT CONCERNS: The patient had a history of left breast cancer, and she underwent left breast-conserving surgery with sentinel lymph node biopsy 2 years ago. She was hospitalized in our center with the complaints of a stomach and lower back pain, which started suddenly and was progressively increased for half a month. DIAGNOSIS: Computed tomography, gastroscopy, and immunohistochemical staining, especially GATA3 and mammaglobin, confirmed that there was simultaneous gastric and adrenal metastases. INTERVENTIONS: She was eligible for the IMpassion131 clinical trials, a Phase 3 randomized, double-blind, placebo-controlled trial under treatment with atezolizumab/palcebo plus paclitaxel as adjuvant-therapy. OUTCOMES: She was still undergoing the therapy and waiting for the further evaluation. LESSONS: In order to better understand metastatic pathways of breast carcinoma, publications of individual patient cases diagnosed with rare metastatic sites should be encouraged, especially for the simultaneous rare metastatic sites. This might improve our understanding of metastatic behavior of breast cancer and promote further clinical research.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/secundario , Neoplasias de la Mama/patología , Neoplasias Gástricas/secundario , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/tratamiento farmacológico , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/tratamiento farmacológico
14.
Br J Nurs ; 29(3): S4-S9, 2020 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-32053446

RESUMEN

Metastatic HER2-positive breast cancer is an incurable disease with a poor prognosis. This article presents a critical appraisal of two treatments commonly used in the treatment of metastatic HER2-positive breast cancer: the oral chemotherapy drug, capecitabine, and the monoclonal antibody, trastuzumab. What follows is a critical discussion of the pharmacotherapeutics of capecitabine and trastuzumab, which considers their use both as single agents and as a combination regimen in the treatment of metastatic breast cancer. The implications of side effects of these drugs are discussed, both individually and in combination, as are the challenges these bring to the prescriber. The article evaluates the use of these agents and concludes that the combination of capecitabine and trastuzumab is an attractive treatment option for patients and for the prescriber.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Capecitabina/uso terapéutico , Trastuzumab/uso terapéutico , Neoplasias de la Mama/patología , Femenino , Humanos , Resultado del Tratamiento
15.
Zhonghua Zhong Liu Za Zhi ; 42(1): 55-60, 2020 Jan 23.
Artículo en Chino | MEDLINE | ID: mdl-32023770

RESUMEN

Objective: To explore the menopausal symptoms and quality of life of hormone receptor positive (HR+ ) breast cancer patients at different endocrine therapy time. Methods: The HR+ breast cancer patients who were pathologically confirmed from 2011 to 2017 in the Sichuan Cancer Hospital were divided into three groups according to endocrine therapy time (<12 months, 12~36 months, >36 months) and analyzed by a cross-sectional study. The Menopausal symptoms and quality of life of these patients were measured using the modified Kupperman scale and the functional assessment of cancer therapy-breast cancer (FACT-B) scale. The differences of menopausal symptoms among different time groups and drug groups were analyzed by Chi-square test. The differences of quality of life and the effects of menopausal symptoms on quality of life were tested by covariance and multiple linear regression analyses. Results: The average score of menopausal symptom of 167 patients was 14.5±7.6 and the prevalence rate was 87.4% (146/167). Among all of the menopausal symptoms, the prevalence rate of insomnia was the highest (73.7%, 123/167). Besides insomnia and excitement, hot flashes was more prevalent in selective estrogen receptor modulator (SERM) users (64.8%, 79/122) , while osteoarthritis was more prevalent in aromatase inhibitor (AI) users (62.2%, 28/45). The total score of FACT-B of Patients was 104.5±15.5, and the compliance rate was up to 89.8% (150/167). However, the condition of each dimension was different, the compliance rates of social/ family and functional dimension were lowest, which were 73.0% (122/167) and 50.9% (85/167), respectively. The menopausal symptoms of patients at different time groups were 15.0±1.3, 14.0±6.9, 14.5±7.4, respectively, and the total score of FACT-B of patients at different time groups were 102.7±17.8, 105.0±12.9, 105.6±16.7, respectively, without significant differences (both P>0.05). Multiple linear regression analysis showed that menopausal symptoms impaired the quality of life of SERM users during the endocrine therapeutic period. The standardized regression coefficients of three time groups were -0.67, -0.30, -0.50, respectively, with the lowest effect on 12~36 months group. Conclusion: HR+ breast cancer patients will have a poor function recovery and social/ family return, who need more attention. Menopausal symptoms are common problems during endocrine therapy, and active measures should be taken to improve patients' quality of life.


Asunto(s)
Inhibidores de la Aromatasa , Neoplasias de la Mama , Calidad de Vida , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/tratamiento farmacológico , Estudios Transversales , Sofocos , Humanos , Menopausia
16.
Anticancer Res ; 40(2): 1079-1085, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32014957

RESUMEN

BACKGROUND/AIM: We evaluated the efficacy of neoadjuvant chemotherapy (NACT) in reducing locally-advanced breast cancer (LABC) size, thus improving breast-conserving surgery (BCS) rates, as well as its long-term outcome. PATIENTS AND METHODS: We analyzed 59 patients treated between 1999-2017 with NACT and subsequent surgery for LABC. RESULTS: We observed a tumor size reduction in 95% of cases, resulting in downstaging in 62.7%. The average tumor shrinkage was 49%. Women with a reduction in tumor size >50% after NACT had better 10-year OS rates than women with a reduction ≤50% (p=0.025). NACT allowed to perform BCS in 44% cases, whereas the remaining 56% cases underwent mastectomy. Overall, we observed recurrences in 37.2% patients. Recurrence rates after BCS and mastectomy were 30.7% (6 loco-regional and 2 distant cases) and 42.4% (5 loco-regional and 9 distant cases), respectively (p=0.07). CONCLUSION: NACT confirmed its effectiveness in reducing mastectomy rates by approximately 50%, without increasing the risk of local or distant recurrences.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
17.
J Photochem Photobiol B ; 204: 111802, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31981990

RESUMEN

Suitable properties as well as eco-friendly synthesis of photoluminescent Au nanoclusters (NCs) make them promising compounds for biomedical diagnostics and visualization applications. However, the potential photochemical activity of such agents on cancerous cells is largely unknown. The nanoclusters (BSA-Au NCs) were synthetized in the presence of BSA (an average hydrodynamic diameter was about 9.4 nm, while the size of the metal cluster was <1.3 nm according to atomic force microscopy measurements) and possessed a broad photoluminescence band at 680 nm in buffered (pH 7.2) aqueous medium. The photochemical activity was studied by adding two fluorescent probes (dihydrorhodamine or Singlet Oxygen Sensor Green) for detection of reactive oxygen species in samples irradiated at 405 nm to minimize direct excitation of the probes. The photoluminescence measurements evidenced the capability of BSA-Au NCs to generate reactive oxygen species upon light exposure, while the observed sensitivity of the photoluminescence properties might be used to indicate photooxidative processes in the medium. The viability test performed on breast cancer cells after incubation with BSA-Au NCs and subsequent irradiation revealed notable difference in induced phototoxicity between two cell lines, which was not the case after the corresponding treatment using the photosensitizer chlorin e6.


Asunto(s)
Oro/química , Nanopartículas del Metal/química , Especies Reactivas de Oxígeno/metabolismo , Albúmina Sérica Bovina/química , Oxígeno Singlete/metabolismo , Animales , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Bovinos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Femenino , Colorantes Fluorescentes/química , Humanos , Láseres de Semiconductores , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/toxicidad , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Especies Reactivas de Oxígeno/química , Oxígeno Singlete/química , Espectrometría de Fluorescencia
18.
J Surg Oncol ; 121(3): 447-455, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31919848

RESUMEN

BACKGROUND: We aim to compare the clinical outcomes of patients with early-stage HER2+ breast cancer treated with adjuvant chemotherapy (AC) and neoadjuvant chemotherapy (NAC). METHODS: Patients with non-metastatic HER2+ breast cancer treated from 2009 to 2018 at our institution comprised our study cohort (n = 1254). Pathologic complete response (pCR) was defined as the absence of invasive disease in the breast and axilla after NAC. Log-rank, Kaplan-Meier, and inverse probability of treatment weighting were used to assess differences in disease-free and overall survival between groups stratified by AC vs. NAC and pCR vs. non-pCR. RESULTS: The majority received AC (n = 787 or 62.8%) while 467 (37.2%) patients received NAC. Median follow up for AC and NAC groups was 46 and 28 months, respectively. The crude disease-free survival and overall survival of our study cohort were 92.2% and 89.1% for AC, 89.1% and 82.2% for NAC pCR, and 68.1% and 60.0% for NAC non-pCR, respectively. For clinical stage ≥IIB patients, NAC conferred a positive but statistically nonsignificant treatment effect over AC in multivariate analysis. CONCLUSIONS: After adjusting for imbalances in our subgroups, we found that, regardless of the sequence of chemotherapy (AC vs. NAC), patients with early-stage HER2+ breast cancer had excellent outcomes.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/mortalidad , Quimioterapia Adyuvante/mortalidad , Terapia Neoadyuvante/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Receptor ErbB-2/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia
19.
Nat Commun ; 11(1): 532, 2020 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-31988290

RESUMEN

Cancer proteogenomics promises new insights into cancer biology and treatment efficacy by integrating genomics, transcriptomics and protein profiling including modifications by mass spectrometry (MS). A critical limitation is sample input requirements that exceed many sources of clinically important material. Here we report a proteogenomics approach for core biopsies using tissue-sparing specimen processing and microscaled proteomics. As a demonstration, we analyze core needle biopsies from ERBB2 positive breast cancers before and 48-72 h after initiating neoadjuvant trastuzumab-based chemotherapy. We show greater suppression of ERBB2 protein and both ERBB2 and mTOR target phosphosite levels in cases associated with pathological complete response, and identify potential causes of treatment resistance including the absence of ERBB2 amplification, insufficient ERBB2 activity for therapeutic sensitivity despite ERBB2 amplification, and candidate resistance mechanisms including androgen receptor signaling, mucin overexpression and an inactive immune microenvironment. The clinical utility and discovery potential of proteogenomics at biopsy-scale warrants further investigation.


Asunto(s)
Neoplasias de la Mama/genética , Proteogenómica/métodos , Receptor ErbB-2/genética , Trastuzumab/uso terapéutico , Biopsia con Aguja Gruesa , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Regulación hacia Abajo , Humanos , Proyectos Piloto , Receptor ErbB-2/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo
20.
Anticancer Res ; 40(1): 229-238, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892571

RESUMEN

BACKGROUND/AIM: We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells. MATERIALS AND METHODS: Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel. RESULTS: Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations. CONCLUSION: Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.


Asunto(s)
Neoplasias de la Mama/patología , Curcumina/farmacología , Progresión de la Enfermedad , Naftoquinonas/farmacología , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/tratamiento farmacológico , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Curcumina/química , Curcumina/uso terapéutico , Matriz Extracelular/metabolismo , Femenino , Humanos , Células MCF-7 , Naftoquinonas/química , Invasividad Neoplásica , Neovascularización Patológica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA