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1.
Isr Med Assoc J ; 21(7): 504, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31507133

RESUMEN

BACKGROUND: Klotho is a transmembrane protein that can be shed and can act as a circulating hormone in three forms: soluble klotho (KL1 + KL2), KL1, and KL2. Klotho was discovered as a gene implicated in aging through inhibition of the IGF-I pathway. Our laboratory discovered the role of klotho as a tumor suppressor in breast cancer and other malignancies. Furthermore, we showed that the KL1 domain mediates this activity. Altered cancer cell metabolism is a hallmark of cancer and our lab demonstrated various effects of klotho on breast cancer cell metabolism. Thus, klotho inhibited glycolysis and activated adenosine monophosphate activating kinase (AMPK), an energy sensor pathway. Moreover, inhibition of AMPK reduced the tumor suppressor activity of klotho. OBJECTIVES: To assess the effect of KL1 on breast tumor cells metabolism, as KL1 possesses the tumor suppressor activity of klotho. METHODS: We used MCF-7 breast cancer cells treated with soluble or over-expressed KL1 and klotho. Glycolysis was assessed by measuring mRNA levels of key glycolytic enzymes using reverse transcription polymerase chain reaction and by measuring lactate and glucose levels in media. The AMPK pathway was studied by monitoring AMPK phosphorylation as well as its down-stream target, acetyl-CoA carboxylase, using western blotting. Wound healing assay was used to assess cell migration. RESULTS: KL1 treatment reduced glycolytic enzymes mRNA levels and the activity of hexokinase, similar to klotho treatment. Furthermore, KL1 reduced glucose uptake and decreased lactate production. KL1 elevated phosphorylated acetyl-CoA carboxylase and phosphorylated AMPK levels. Inhibition AMPK (using a mutant AMPK activator) stopped KL1 from inhibiting cell migration, suggesting AMPK underlies klotho's tumor suppressor activity. CONCLUSIONS: Our data indicate KL1 as a regulator of metabolic activity in breast cancer and suggest that metabolic alterations underlie KL1 tumor suppressor activities. Furthermore, as KL1 and klotho share a similar effect on cell metabolism, our results further support the central role KL1 domain plays in klotho's tumor suppressor activity.


Asunto(s)
Neoplasias de la Mama/metabolismo , Glucuronidasa/metabolismo , Glucólisis/fisiología , Proteínas Quinasas Activadas por AMP/metabolismo , Movimiento Celular/fisiología , Femenino , Humanos , Células MCF-7 , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
2.
Medicine (Baltimore) ; 98(37): e17114, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31517847

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Cisplatino/normas , Adulto , Cisplatino/uso terapéutico , Femenino , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Resultado del Tratamiento
3.
Pharm Res ; 36(11): 154, 2019 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-31482205

RESUMEN

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.


Asunto(s)
Antineoplásicos/química , Neoplasias de la Mama/tratamiento farmacológico , Dendrímeros/química , Docetaxel/química , Paclitaxel/química , Receptor ErbB-2/metabolismo , Trastuzumab/química , Antineoplásicos/farmacología , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Docetaxel/farmacología , Interacciones de Drogas , Liberación de Fármacos , Colorantes Fluorescentes/química , Humanos , Paclitaxel/farmacología , Propiedades de Superficie , Trastuzumab/farmacología , Resultado del Tratamiento
5.
JAMA ; 322(9): 868-886, 2019 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-31479143

RESUMEN

Importance: Medications to reduce risk of breast cancer are effective for women at increased risk but also cause adverse effects. Objective: To update the 2013 US Preventive Services Task Force systematic review on medications to reduce risk of primary (first diagnosis) invasive breast cancer in women. Data Sources: Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE, and MEDLINE (January 1, 2013, to February 1, 2019); manual review of reference lists. Study Selection: Discriminatory accuracy studies of breast cancer risk assessment methods; randomized clinical trials of tamoxifen, raloxifene, and aromatase inhibitors for primary breast cancer prevention; studies of medication adverse effects. Data Extraction and Synthesis: Investigators abstracted data on methods, participant characteristics, eligibility criteria, outcome ascertainment, and follow-up. Results of individual trials were combined by using a profile likelihood random-effects model. Main Outcomes and Measures: Probability of breast cancer in individuals (area under the receiver operating characteristic curve [AUC]); incidence of breast cancer, fractures, thromboembolic events, coronary heart disease events, stroke, endometrial cancer, and cataracts; and mortality. Results: A total of 46 studies (82 articles [>5 million participants]) were included. Eighteen risk assessment methods in 25 studies reported low accuracy in predicting the probability of breast cancer in individuals (AUC, 0.55-0.65). In placebo-controlled trials, tamoxifen (risk ratio [RR], 0.69 [95% CI, 0.59-0.84]; 4 trials [n = 28 421]), raloxifene (RR, 0.44 [95% CI, 0.24-0.80]; 2 trials [n = 17 806]), and the aromatase inhibitors exemestane and anastrozole (RR, 0.45 [95% CI, 0.26-0.70]; 2 trials [n = 8424]) were associated with a lower incidence of invasive breast cancer. Risk for invasive breast cancer was higher for raloxifene than tamoxifen in 1 trial after long-term follow-up (RR, 1.24 [95% CI, 1.05-1.47]; n = 19 747). Raloxifene was associated with lower risk for vertebral fractures (RR, 0.61 [95% CI, 0.53-0.73]; 2 trials [n = 16 929]) and tamoxifen was associated with lower risk for nonvertebral fractures (RR, 0.66 [95% CI, 0.45-0.98]; 1 trial [n = 13 388]) compared with placebo. Tamoxifen and raloxifene were associated with increased thromboembolic events compared with placebo; tamoxifen was associated with more events than raloxifene. Tamoxifen was associated with higher risk of endometrial cancer and cataracts compared with placebo. Symptomatic effects (eg, vasomotor, musculoskeletal) varied by medication. Conclusions and Relevance: Tamoxifen, raloxifene, and aromatase inhibitors were associated with lower risk of primary invasive breast cancer in women but also were associated with adverse effects that differed between medications. Risk stratification methods to identify patients with increased breast cancer risk demonstrated low accuracy.


Asunto(s)
Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/prevención & control , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/uso terapéutico , Adulto , Área Bajo la Curva , Inhibidores de la Aromatasa/efectos adversos , Neoplasias de la Mama/genética , Femenino , Genes BRCA1 , Genes BRCA2 , Humanos , Mutación , Guías de Práctica Clínica como Asunto , Clorhidrato de Raloxifeno/efectos adversos , Clorhidrato de Raloxifeno/uso terapéutico , Medición de Riesgo/métodos , Factores de Riesgo , Moduladores Selectivos de los Receptores de Estrógeno/efectos adversos , Tamoxifeno/efectos adversos
6.
JAMA ; 322(9): 857-867, 2019 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-31479144

RESUMEN

Importance: Breast cancer is the most common nonskin cancer among women in the United States and the second leading cause of cancer death. The median age at diagnosis is 62 years, and an estimated 1 in 8 women will develop breast cancer at some point in their lifetime. African American women are more likely to die of breast cancer compared with women of other races. Objective: To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on medications for risk reduction of primary breast cancer. Evidence Review: The USPSTF reviewed evidence on the accuracy of risk assessment methods to identify women who could benefit from risk-reducing medications for breast cancer, as well as evidence on the effectiveness, adverse effects, and subgroup variations of these medications. The USPSTF reviewed evidence from randomized trials, observational studies, and diagnostic accuracy studies of risk stratification models in women without preexisting breast cancer or ductal carcinoma in situ. Findings: The USPSTF found convincing evidence that risk assessment tools can predict the number of cases of breast cancer expected to develop in a population. However, these risk assessment tools perform modestly at best in discriminating between individual women who will or will not develop breast cancer. The USPSTF found convincing evidence that risk-reducing medications (tamoxifen, raloxifene, or aromatase inhibitors) provide at least a moderate benefit in reducing risk for invasive estrogen receptor-positive breast cancer in postmenopausal women at increased risk for breast cancer. The USPSTF found that the benefits of taking tamoxifen, raloxifene, and aromatase inhibitors to reduce risk for breast cancer are no greater than small in women not at increased risk for the disease. The USPSTF found convincing evidence that tamoxifen and raloxifene and adequate evidence that aromatase inhibitors are associated with small to moderate harms. Overall, the USPSTF determined that the net benefit of taking medications to reduce risk of breast cancer is larger in women who have a greater risk for developing breast cancer. Conclusions and Recommendation: The USPSTF recommends that clinicians offer to prescribe risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women who are at increased risk for breast cancer and at low risk for adverse medication effects. (B recommendation) The USPSTF recommends against the routine use of risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, in women who are not at increased risk for breast cancer. (D recommendation) This recommendation applies to asymptomatic women 35 years and older, including women with previous benign breast lesions on biopsy (such as atypical ductal or lobular hyperplasia and lobular carcinoma in situ). This recommendation does not apply to women who have a current or previous diagnosis of breast cancer or ductal carcinoma in situ.


Asunto(s)
Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/prevención & control , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/uso terapéutico , Adulto , Neoplasias de la Mama/genética , Femenino , Genes BRCA1 , Genes BRCA2 , Humanos , Persona de Mediana Edad , Mutación , Clorhidrato de Raloxifeno/uso terapéutico , Medición de Riesgo/métodos , Factores de Riesgo
7.
Anticancer Res ; 39(9): 4941-4945, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519599

RESUMEN

AIM: This study describes the demographic, socioeconomic, and tumor-specific characteristics of patients who refuse breast cancer surgery. MATERIALS AND METHODS: This is a retrospective study of breast cancer patients from 2004-2015 captured by the National Cancer Data Base. Demographic, socioeconomic, and tumor-specific predictors were compared between patients who refused breast cancer surgery versus those who agreed to surgery, using bivariate and multivariate models. RESULTS: A total of 2,445,870 patients met the inclusion criteria. On multivariate analysis, black and Asian patients had higher odds of refusing surgical treatment compared to whites (OR=2.16, CI=2.05-2.28, p<0.001), (OR=1.58, CI=1.41-1.76, p<0.001), respectively. Moreover, patients with government insurance (OR=1.97, CI=1.86-2.09, p<0.001) and uninsured patients (OR=3.91, CI=3.50-4.36, p<0.001) were found to have higher odds of surgical treatment refusal when compared to patients with private insurance. CONCLUSION: Specific demographic and disease-specific characteristics are related to refusing potentially life-saving breast cancer surgery.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mamografía , Persona de Mediana Edad , Estadificación de Neoplasias , Oportunidad Relativa , Estudios Retrospectivos , Factores Socioeconómicos , Evaluación de Síntomas , Negativa del Paciente al Tratamiento , Estados Unidos/epidemiología , Adulto Joven
8.
Anticancer Res ; 39(9): 4957-4963, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519601

RESUMEN

BACKGROUND/AIM: Adjuvant radiotherapy (RT) damages multiple layers of skin, muscle, blood vessels and blood cells that are included within the RT area. Indirect, bystander systemic effects could also develop in cells not directly hit by radiation. MATERIALS AND METHODS: Ninety-three female patients recovering from breast cancer surgery and 82 female healthy blood donors were analyzed. For identification of systemic adaptive and innate immune response, rapid and low-cost blood-based biomarkers were assayed. RESULTS: Post-operated breast cancer patients had a decreased number of circulating adaptive immune response cells but increased number of circulating immunosuppressive myeloid subpopulations. RT decreased the number of T-cells and platelets without influencing the number of immunosuppressive myeloid subpopulations. Alterations in the number and phenotypes of T-cell subpopulations were associated with SNPs. CONCLUSION: The combination of RT and immunotherapy might provide optimal treatment for cancer patients.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Inmunidad Celular/genética , Inmunidad Celular/efectos de la radiación , Recuento de Leucocitos , Fenotipo , Polimorfismo de Nucleótido Simple , Inmunidad Adaptativa , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Estudios de Casos y Controles , Femenino , Humanos , Inmunidad Innata , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Radioterapia Ayuvante , Linfocitos T/inmunología , Linfocitos T/metabolismo
9.
Anticancer Res ; 39(9): 4971-4975, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519603

RESUMEN

BACKGROUND/AIM: We evaluated the incidence of uterine and breast cancer among women diagnosed with granulosa cell tumors (GCTs) of the ovary. PATIENTS AND METHODS: The US Surveillance, Epidemiology, and End Results (SEER) database was accessed and patients diagnosed with a GCT and had a known follow-up between 1973-2014 were identified. Personal tumor history was extracted and patients with a previous or subsequent malignant breast or uterine tumor were identified. The expected incidence of breast and uterine cancer was calculated based on the U.S age-specific rate of breast and uterine cancer per 100,000 women. Standardized incidence ratio (SIR) with 95% confidence intervals (95% CI) were calculated for each tumor. RESULTS: A total of 1908 cases of GCT were identified. Seventy- nine (4.14%) and 53 (2.78%) patients were diagnosed with a malignant breast and uterine malignancy. The cumulative expected number of malignant breast and uterine tumors was 27 (1.41%) and 6 (0.31%), respectively. The calculated SIR for breast and uterine malignancies was 2.96 (95%CI=2.34, 3.68) and 8.83 (95%CI=6.61, 11.56), respectively. CONCLUSION: An increased incidence of breast and uterine malignancies among patients diagnosed with GCTs was observed.


Asunto(s)
Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/etiología , Tumor de Células de la Granulosa/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Neoplasias Uterinas/epidemiología , Neoplasias Uterinas/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Programa de VERF , Estados Unidos/epidemiología , Adulto Joven
10.
Anticancer Res ; 39(9): 5009-5018, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519608

RESUMEN

BACKGROUND/AIM: Interleukin (IL)-18, which belongs to the IL-1 superfamily of cytokines, is a known interferon-gamma (IFN-γ)-inducing factor. Since IFN-γ plays an essential role in anticancer immunity mediated through cytotoxic T cells, IL-18 may also contribute to the function of immunosurveillance. The aim of the study was to examine the association of IL-18 with the outcomes of patients with breast cancer. PATIENTS AND METHODS: Serum IL-18 levels were determined at baseline in 270 patients operated for breast cancer, and the relapse-free survival (RFS) was compared between IL-18-high and -low groups. The relationships between IL-18 and tumor-infiltrating lymphocytes (TILs) or the neutrophil-to-lymphocyte ratio (NLR) were also investigated. RESULTS: The RFS of patients was significantly better in the IL-18-low group than in the IL-18-high group (p=0.032). According to the multivariate analysis, IL-18 was a significant and independent predictive factor for RFS (hazard ratio(HR)=0.336; 95% confidence interval(CI)=0.147-0.727; p=0.0053). No association was observed between the IL-18 levels and TILs or NLRs. CONCLUSION: IL-18 levels may be useful for predicting the prognosis of patients who have received surgical treatment for breast cancer.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama/sangre , Neoplasias de la Mama/mortalidad , Interleucina-18/sangre , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Citocinas/sangre , Citocinas/metabolismo , Femenino , Humanos , Recuento de Leucocitos , Recuento de Linfocitos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neutrófilos/inmunología , Neutrófilos/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Valores de Referencia , Estudios Retrospectivos , Carga Tumoral
14.
Medicine (Baltimore) ; 98(36): e15719, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31490359

RESUMEN

BACKGROUND: We evaluated the relationship between the age at first use of oral contraceptives (OC) and breast cancer (BC) risk. METHODS: We searched PubMed, Embase, and related reviews published through June 28, 2018, and used summary relative risk (RR) and 95% confidence intervals (CIs) to evaluate the cancer risks, and fixed-effects dose-response meta-analysis to assess potential linear and non-linear dose-response relationships. RESULTS: We included 10 studies, with 8585 BC cases among 686,305 participants. The pooled RR for BC was 1.24 (95% CI: 1.10-1.41), with moderate heterogeneities (I = 66.5%, P < .001). No significant publication bias was found (P = .584 for Begg test, P = .597 for Egger test). A linear dose-response relationship between the age at first OC use and BC risk was detected (P = .518 for non-linearity). Subgroup analyses were restricted to studies done by BC subtypes, region, sample size, follow-up time and study quality. Inconsistent consequences with no statistical significance were explored when limited to studies from Western countries, study quality <7, sample size <10,000, follow-up time <5 years, and BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) expression status in tumor tissue. Sensitivity analyses indicated that our results were stable and reliable after removing each study in turn and omitting studies of adjusted unreported variables. CONCLUSION: A significant linear relationship between the age at first OC use and BC risk was confirmed. No further consistent differences are noted in multiple aspects of BC subtypes defined by progesterone or ER status.


Asunto(s)
Neoplasias de la Mama/epidemiología , Anticonceptivos Orales/administración & dosificación , Factores de Edad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Receptor ErbB-2/biosíntesis , Receptores Estrogénicos/biosíntesis , Receptores de Progesterona/biosíntesis , Factores de Riesgo
15.
Medicine (Baltimore) ; 98(36): e16937, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31490377

RESUMEN

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.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Moléculas de Adhesión Celular/biosíntesis , Receptor ErbB-2/biosíntesis , Trastuzumab/uso terapéutico , Adulto , Factores de Edad , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Receptores Estrogénicos/biosíntesis , Receptores de Progesterona/biosíntesis
16.
Medicine (Baltimore) ; 98(36): e17009, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31490383

RESUMEN

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.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos Fitogénicos/análisis , Neoplasias de la Mama/tratamiento farmacológico , Erythrina/química , Aceites Volátiles/uso terapéutico , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Transición Epitelial-Mesenquimal/efectos de los fármacos , Humanos , Células MCF-7 , Aceites Volátiles/química , Aceites Volátiles/aislamiento & purificación , Aceites Volátiles/farmacología , Fitoterapia , Hojas de la Planta/química
17.
Anticancer Res ; 39(9): 5135-5142, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31519625

RESUMEN

AIM: To compare the overall survival (OS) of patients with locoregional and metastatic breast cancer (BC) considering baseline demographic, clinical and contextual characteristics. MATERIALS AND METHODS: A retrospective analysis of a cancer registry was conducted, using the Kaplan-Meier and Mantel-Cox analyses for the calculation of median OS and cumulative survival. RESULTS: The median OS was 112 months, being longer in patients with locoregional versus those with metastatic BC at diagnosis (115 vs. 31 months, p<0.001). The cumulative survival at 1, 3 and 5 years were 94.9%, 85.6% and 76.5%, respectively. More recent year of diagnosis [hazard ratio (HR)=1.09] and age at diagnosis (≥65 vs. 40 years, HR=2.79) and presence of metastatic disease (HR=5.69) were associated with a shorter OS. The region of residence, morphology and topography of the tumor were also associated with survival in patients with BC. Rurality was only associated with lower survival in patients with metastatic BC. CONCLUSION: This study identified significant differences in the median OS of patients with locoregional and those with metastatic BC considering their baseline characteristics.


Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/terapia , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Adulto Joven
20.
Pol J Pathol ; 70(2): 91-99, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31556559

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Terapia Neoadyuvante , Clasificación del Tumor , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama/cirugía , Femenino , Humanos , Antígeno Ki-67/metabolismo , Estudios Prospectivos , Receptores Estrogénicos/metabolismo , Receptores de Progesterona/metabolismo , Resultado del Tratamiento
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