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1.
Neurourol Urodyn ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38979850

RESUMEN

OBJECTIVES: This study aimed to assess the efficacy and safety of monoclonal antibody therapies (MATs) for interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A systematic search was conducted across databases including PubMed, Embase, clinicalTrial.gov, and the Cochrane Library Central Register of Controlled Trials. Randomized controlled trials (RCTs) comparing MATs versus placebo were included. Primary outcomes comprised the Global Response Assessment (GRA) scale and the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI). Additional analyses encompassed mean daily frequency of voids, the O'Leary-Sant Interstitial Cystitis Problem Index, pain scores, and complications. Statistical analyses were performed using Review Manager 5.3. RESULTS: Five high-quality RCTs, comprising 263 patients with IC/BPS, were ultimately selected. MATs were generally effective in treating IC/BPS. Patients receiving MATs exhibited a higher satisfaction rate (odds ratio [OR]: 2.7, confidence interval [CI]: 1.31-5.58, p = 0.007) and lower ICSI scores (mean difference [MD]: -1.44, CI: -2.36 to -0.52, p = 0.002). Moreover, MAT recipients experienced reduced pain (MD: -0.53, CI: -0.79 to -0.26, p < 0.0001) and decreased frequency of urination (MD: -1.91, CI: -2.55 to -1.27, p < 0.00001). Importantly, there were no disparities regarding complication incidence in the MAT and control groups. CONCLUSIONS: The current findings indicate that MATs are effective and safe for treating IC/BPS. Nonetheless, future RCTs with larger sample sizes and long-term follow-up are warranted.

2.
Cancer Cell Int ; 19: 165, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31244553

RESUMEN

BACKGROUND: Enhanced glycolysis in tumors, known as the Warburg effect, provides the metabolic basis of enhanced cancer cell proliferation and metastasis. The Warburg pathway enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a newly identified key kinase that regulates transcriptional reprogramming and cell proliferation. Here we show the prognostic value of PFKFB4 expression in patients with operable breast cancer. METHODS: PFKFB4 expression was evaluated by immunohistochemistry in surgical specimens retrospectively collected from 200 patients with histologically proven invasive ductal breast cancer. Kaplan-Meier survival analysis and Cox regression analysis were performed to assess the prognostic significance of PFKFB4 expression. RESULTS: Kaplan-Meier survival analysis revealed that breast cancer patients with high PFKFB4 expression demonstrated unfavorable disease-free survival (p = 0.008) and overall survival (p = 0.002). PFKFB4 had an hazard ratio (HR) of 7.38 (95% CI 1.69-32.3; p = 0.008) in univariate Cox analysis and retained prognostic power (HR 7.44, 95% CI 1.67-33.2; p = 0.009) when adjusted by tumor size, lymph node status, grade, estrogen receptor status, human epidermal growth factor receptor 2 status and subtype, which indicated PFKFB4 was an independent prognostic factor in breast cancer. CONCLUSIONS: Together, our findings establish the prognostic value of metabolic enzyme PFKFB4 in patients with operable breast cancer.

3.
Arterioscler Thromb Vasc Biol ; 34(4): 946-51, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24371085

RESUMEN

OBJECTIVE: The presence of silent cerebral infarction (SCI) increases the risk of transient ischemia attack, symptomatic stroke, cardiovascular disease, and dementia. Total bilirubin (TB) levels were demonstrated to be decreased in carotid intima-media thickness, cardiovascular disease, stroke, and peripheral arterial disease. However, little information is available concerning the correlation between TB and SCI. APPROACH AND RESULTS: A cross-sectional study was conducted to evaluate the association between TB and SCI in 2865 subjects (1831 men and 1034 women) undergoing medical checkup. The participants with SCI had lower TB levels than those without SCI. The subjects with a low TB had a higher prevalence of SCI. Moreover, partial correlation showed that TB levels were tightly correlated with brachial-ankle pulse wave velocity after adjusting for confounding covariates (r=-0.149; P<0.001). Multivariate logistic regression analysis revealed that higher TB was associated with a lower risk of SCI (odds ratio, 0.925; 95% confidence interval, 0.897-0.954; P<0.001). CONCLUSIONS: TB is a novel biochemical indicator for SCI regardless of classical cardiovascular risk factors. Early measurement of TB may be useful to assess the risk of SCI.


Asunto(s)
Bilirrubina/sangre , Infarto Cerebral/sangre , Adulto , Anciano , Índice Tobillo Braquial , Enfermedades Asintomáticas , Biomarcadores/sangre , Infarto Cerebral/diagnóstico , Infarto Cerebral/epidemiología , Distribución de Chi-Cuadrado , China/epidemiología , Estudios Transversales , Regulación hacia Abajo , Femenino , Humanos , Modelos Logísticos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Prevalencia , Análisis de la Onda del Pulso , Factores de Riesgo
4.
J Spinal Disord Tech ; 28(1): E30-4, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25075988

RESUMEN

STUDY DESIGN: A cross-sectional study in a general health examination. OBJECTIVE: To investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and lumbar disk herniation (LDH). SUMMARY OF BACKGROUND DATA: Lumbar disk herniation (LDH) is a major cause of low back pain and sciatica. Various vascular risk factors such as obesity, diabetes mellitus, and smoking have been reported to be associated with LDH. BaPWV is an early indicator of subclinical atherosclerosis. METHODS: A total of 490 participants with LDH and 490 participants without LDH were selected for the evaluation of baPWV. BaPWV was measured using an automatic device. The prevalence of LDH was calculated by the quartiles of baPWV levels. Multiple linear regression analysis was performed to evaluate the risk factors for baPWV. RESULTS: LDH patients had significantly higher readings of baPWV compared with non-LDH subjects (P<0.001). The prevalence rate of LDH gradually increased according to baPWV quartiles. In addition, the levels of baPWV tended to increase as the frequency of physical activity reduced. Multiple linear regression analysis showed that body mass index, low-density lipoprotein cholesterol, physical activity, and systolic blood pressure contributed to increased baPWV. CONCLUSIONS: The findings showed that LDH patients had higher baPWV levels. In addition, reduced physical activity was a risk factor contributing to increased baPWV. Further studies are warranted to determine the role of baPWV in LDH.


Asunto(s)
Desplazamiento del Disco Intervertebral/fisiopatología , Vértebras Lumbares/fisiopatología , Actividad Motora , Rigidez Vascular/fisiología , Adulto , Anciano , Índice Tobillo Braquial , Estudios Transversales , Femenino , Humanos , Desplazamiento del Disco Intervertebral/epidemiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Análisis de la Onda del Pulso , Análisis de Regresión
5.
Breast Cancer Res Treat ; 145(2): 349-58, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24781973

RESUMEN

Glucose-regulated protein (GRP) 78 and C/-EBP homologous protein (CHOP) are commonly used as markers of endoplasmic reticulum (ER) stress. As an ER chaperone, GRP78 functions as a potent anti-apoptotic factor and confers drug resistance, whereas CHOP is a key initiating factor of ER stress-related cell death. We aimed at investigating the predictive values of GRP78 and CHOP in breast cancer patients who underwent adjuvant chemotherapy. An immunohistochemistry screen for GRP78 and CHOP was performed using a tissue microarray containing 250 tumors from female patients diagnosed with invasive ductal breast carcinoma at the Fudan University Shanghai Cancer Center. The staining results were scored semi-quantitatively, and a prediction model was constructed to verify the hypothesis. In this retrospective cohort study, CHOP correlated with prolonged disease-free survival (HR = 0.385, 95 % CI 0.215-0.688; P = 0.001), whereas GRP78 showed an opposite association (HR = 4.573; 95 % CI 2.291-9.128; P < 0.001). Moreover, in a GRP78-positive subset, CHOP overexpression correlated with a lower risk of recurrence. In the receiver operating characteristic analysis, the prediction capability of the predictive model combining the above two markers surpassed that of the traditional model (P = 0.0085 for the area under the curve comparison). Within the anthracycline-treatment subgroup, the combined GRP78 and CHOP exhibited similar predictive significance. Cumulatively, our findings suggest a tight association between ER stress markers and clinical outcomes for patients with breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Estrés del Retículo Endoplásmico , Proteínas de Choque Térmico/metabolismo , Factor de Transcripción CHOP/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Antraciclinas/uso terapéutico , Antibióticos Antineoplásicos/uso terapéutico , Biomarcadores/análisis , Biomarcadores/metabolismo , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Chaperón BiP del Retículo Endoplásmico , Femenino , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Análisis de Matrices Tisulares
6.
Respiration ; 88(1): 31-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24854778

RESUMEN

BACKGROUND: Systemic inflammation is related to disease progression in asthma. Activated platelets play a critical role in atherogenesis, inflammation, and atherothrombosis. The mean platelet volume (MPV) is an early marker of platelet activation. OBJECTIVES: The aim of this study is to clarify the relevance of MPV levels in patients with stable and exacerbated asthma. METHODS: We investigated the peripheral blood cell count parameters, C-reactive protein (CRP), lung function parameters, and arterial blood gas in patients with asthma and control subjects. Eighty-five stable asthma patients and 85 asthmatics with exacerbations were investigated. Eighty-five controls matched for age, gender, body mass index (BMI), and smoking status were recruited. RESULTS: Patients with exacerbated asthma had lower MPV and higher CRP levels and white blood cell (WBC) counts compared to patients with stable asthma and control subjects. Furthermore, the MPV was reduced in patients with stable asthma compared to control subjects. Negative correlations between MPV and CRP were present in stable and exacerbated asthma. Although there was no relationship between MPV and WBC count in stable asthma, there was an inverse relationship between MPV and WBC count in exacerbated asthma. CONCLUSIONS: These findings show that patients with stable asthma had a lower MPV compared to controls and the MPV levels in asthmatic patients with exacerbations were lower compared to those in patients with stable asthma. Further investigations regarding the role of MPV in asthma may be beneficial in the search for therapeutic targets.


Asunto(s)
Asma/sangre , Volúmen Plaquetario Medio , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fumar
7.
Contemp Oncol (Pozn) ; 18(1): 22-8, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24876817

RESUMEN

AIM OF THE STUDY: To explore the mechanism of oxidative stress in the development of prostate cancer, here we compared 4-hydroxynonenal (4-HNE)- treated LNCaP (hormone-sensitive) and DU145 (hormone insensitive) cells with significant differences in sensitivity to androgen. MATERIAL AND METHODS: The prostate cancer cell line LNCaP and late cell line DU145 were treated with different concentrations of 4-HNE. The cell proliferation, apoptosis and mitochondrial transmembrane potential were detected at different time points, and expression of related molecules in cell proliferation and apoptosis signal pathway was analyzed by Western blot, and the over-expression of glutathione S-transferase (GSTA-4) was used to validate the changes of the effects of 4-HNE on the two kinds of cells. RESULTS: LNCaP cells showed greater antiproliferative and proapoptotic activities of HNE in a time- and dose-dependent manner corresponding to the activation of p53-mediated intrinsic apoptotic signaling, but JNK activation was not observed. In contrast, HNE-treated DU145 cells showed less apoptosis and proliferation was not inhibited; instead there was sustained activation of JNK, but activation of p53, p-p53, p21, Bax and caspase-3 was not observed. In addition, their effect of induction of apoptosis can be inhibited by overexpression of GSTA-4. CONCLUSIONS: These studies suggest that 4-HNE promotes prostate cancer cell apoptosis through the p53 signaling pathway; the differences of sensitivity to 4-HNE in LNCaP and DU145 cells may be related to the androgen sensitivity of prostate cancer cells; and the 4-HNE-induced p53-mediated apoptosis signal is regulated by GSTA-4.

8.
Respirology ; 18(8): 1244-8, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23786593

RESUMEN

BACKGROUND AND OBJECTIVE: An increased mean platelet volume (MPV) is an early marker of platelet activation. Activated platelets play a role in atherogenesis, inflammation and atherothrombosis. Chronic obstructive pulmonary disease (COPD) is associated with cardiovascular disease-related mortality. The aim of the study is to measure the MPV in patients with stable and exacerbated COPD. METHODS: We investigated the peripheral blood cell count parameters, C-reactive protein (CRP), fibrinogen, lung function parameters and arterial blood gas analysis in patients with COPD and in controls. Seventy participants were investigated at admission for an acute exacerbation of COPD and reassessed when stable. Seventy controls were matched for age, gender, body mass index, medication use and smoking. RESULTS: Participants with an exacerbation of COPD had lower MPV and higher CRP, white blood cells (WBC) and fibrinogen compared with when in stable phase of COPD and controls. MPV was also lower in patients in stable phase COPD compared with controls. Negative correlations between MPV and CRP, and between MPV and platelet count were present in patients in stable and exacerbation of COPD. CONCLUSIONS: The findings show that COPD patients, during acute exacerbation and in stable phase, have lower MPV compared with healthy controls; the MPV increase once patients have recovered from their exacerbation of COPD.


Asunto(s)
Progresión de la Enfermedad , Volúmen Plaquetario Medio , Enfermedad Pulmonar Obstructiva Crónica/sangre , Índice de Severidad de la Enfermedad , Anciano , Recuento de Células Sanguíneas , Análisis de los Gases de la Sangre , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Fibrinógeno/metabolismo , Humanos , Masculino , Persona de Mediana Edad
9.
Chin J Cancer ; 32(9): 520-3, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23544448

RESUMEN

At present, approximately 20% of Hodgkin lymphomas (HL) are relapsed and refractory, and therapeutic methods including chemotherapy, radiotherapy, and even stem cell transplantation are unsatisfactory. Brentuximab vedotin, composed of CD30 antibody and a chemotherapeutic agent, is a new targeted drug that eradicates tumor cells by binding to the CD30 antigen on their surface. In clinical trials, the response rate and complete remission rate of this drug were 73% and 40%, respectively, for relapsed and refractory HL. Here we report a case of CD30-positive relapsed and refractory HL that was treated with brentuximab. Before the treatment with brentuximab, the patient underwent chemotherapy, radiotherapy, and autologous stem cell transplantation. However, the disease continued to progress, affecting multiple organs and prompting symptoms such as persistent fever. After the treatment with brentuximab, the patient's condition improved. Body temperature returned to normal after 4 days. Lung nodules were reduced in size and number after a single course of treatment, and PET/CT showed partial remission and complete remission after 3 and 6 courses of treatment, respectively. The entire treatment process progressed smoothly, though the patient experienced some symptoms due to chemotherapy, including peripheral neuritis of the limbs, irritating dry cough, and mild increase in aminotransferase. No serious adverse effects were observed. The current general condition of the patient is good; the continuous complete remission has amounted to 6 months.


Asunto(s)
Antineoplásicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Adolescente , Brentuximab Vedotina , Femenino , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/metabolismo , Enfermedad de Hodgkin/patología , Enfermedad de Hodgkin/terapia , Humanos , Antígeno Ki-1/metabolismo , Recurrencia Local de Neoplasia , Factor de Transcripción PAX5/metabolismo , Tomografía de Emisión de Positrones , Trasplante de Células Madre , Tomografía Computarizada por Rayos X
10.
J Virol Methods ; 299: 114343, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34728269

RESUMEN

Bovine respiratory disease complex (BRDC) is a serious disease affecting feedlot cattle in China and likely other places worldwide. Bovine viral diarrhea virus (BVDV) and bovine parainfluenza virus type 3 (BPIV3) are principally responsible for causing BRDC, and are a major strain to the industrial economy. Eradication of these viruses/disease requires swift viral identification and treatment. Hence, this study established a fast and easy procedure of BVDV and BPIV3 identification that employs reverse transcription recombinase polymerase amplification (RT-RPA) and lateral flow dipstick (LFD), and uses primers and lateral flow (LF) probe targeting the 5'-UTR gene of BVDV and phosphoprotein P gene of BPIV3, respectively. Our assay was able to successfully amplify BVDV and BPIV3 RNA within 25 min at 35 °C using RT-RPA, with products visible on the LFD within 5 min at room temperature (RT). The lowest detection limits were 50 RNA molecules for BVDV and 34 RNA molecules for BPIV3 per reaction. We also demonstrated that the established dual RT-RPA LFD assay was precise and targeted, harboring excellent potential to become an onsite molecular diagnostic tool in the detection of BVDV and BPIV3. This method can detect BVDV (Pestivirus A, B) and BPIV3, and exhibit no cross-reaction with other viruses like the classical swine fever virus (CSFV) and infectious bovine rhinotracheitis virus (IBRV). The assay performance was further assessed with clinical samples, and demonstrated good performance in comparison to real-time RT-PCR (RT-qPCR). Moreover, the RT-RPA LFD assay was comparitively rapid and required minimal training.


Asunto(s)
Recombinasas , Transcripción Reversa , Animales , Bovinos , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Recombinasas/genética , Sensibilidad y Especificidad , Porcinos
11.
Zhonghua Nan Ke Xue ; 17(10): 894-6, 2011 Oct.
Artículo en Zh | MEDLINE | ID: mdl-22049791

RESUMEN

OBJECTIVE: To evaluate the efficacy of tadalafil in the treatment of ED after transurethral resection of the prostate (TURP). METHODS: A total of 113 patients with ED after TURP received 3 months of tadalafil treatment and were followed up for 6 months. The IIEF-5 scores of the patients and the number of successful penile intromissions and sustained penile erections in the patients' sexual life diary were compared before and after the treatment. RESULTS: The IIEF-5 scores were 9.83 +/- 3.96 before the medication, 20.23 +/- 3.25 after it, and 17.28 +/- 3.03 at 6 months after drug withdrawal, with statistically significant differences between pre- and post-treatment (P < 0.05). The patients' success rates of penile intromission and sexual intercourse were increased from 44.8% and 7.5% before the medication to 81.7% and 63.2% after it. CONCLUSION: Tadalafil can be used as a first-line drug for the treatment of ED after TURP.


Asunto(s)
Carbolinas/uso terapéutico , Disfunción Eréctil/tratamiento farmacológico , Inhibidores de Fosfodiesterasa/uso terapéutico , Resección Transuretral de la Próstata/efectos adversos , Anciano , Disfunción Eréctil/etiología , Humanos , Masculino , Persona de Mediana Edad , Tadalafilo , Resultado del Tratamiento
12.
Breast Cancer Res Treat ; 124(2): 419-24, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20300826

RESUMEN

In this article, inconsistency of the association of polymorphisms of fibroblast growth factor receptor 2 (FGFR2) with breast cancer is noted. Three commonly studied FGFR2 polymorphisms including rs1219648 (A > G), rs2420946 (C > T), and rs2981582 (C > T) were selected to explore their association with risk of development of breast cancer by meta-analysis of published case-control studies. The results showed that all these three polymorphisms were significantly associated with altered breast cancer risk in any model (co-dominant, dominant, or recessive model) and in stratification based on ethnicity and study design. In the subgroup analyses for postmenopausal women, significantly increased risks were found for rs1219648 and rs2420946 in any model. This meta-analysis suggests that FGFR2 is likely an important genetic marker contributing to susceptibility of breast cancer. We recommend that these single nucleotide polymorphisms to be included in future association studies and functional assays.


Asunto(s)
Neoplasias de la Mama/genética , Polimorfismo de Nucleótido Simple , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Estudios de Casos y Controles , Medicina Basada en la Evidencia , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Humanos , Oportunidad Relativa , Medición de Riesgo , Factores de Riesgo
13.
Zhonghua Yi Xue Za Zhi ; 90(40): 2823-5, 2010 Nov 02.
Artículo en Zh | MEDLINE | ID: mdl-21162791

RESUMEN

OBJECTIVE: To assess the correlation between metabolic syndrome and clinical progression in patients with benign prostatic hyperplasia (BPH). METHODS: A total of 382 BPH patients with lower urinary tract symptoms were divided into two groups according to whether or not there was a diagnosis of metabolic syndrome (MS). MS was defined by the International Diabetes Federation (IDF) in 2005. Abdominal B-ultrasound was used to measure the total volume of prostate (TP) and its average annual growth rate was calculated. Body mass index, waist-hip ratio, blood biochemistry, blood pressure, blood glucose and other indicators were compared in these two groups of patients with regards to the clinical progression associated with BPH. RESULTS: A total of 187 MS cases were found in 382 (48.59%) BPH patients. It showed a higher body mass index, high glycemia, high triglycerides, high blood pressure and high IPSS, TP and PSA levels. Also it showed a higher occurrence of surgical rate (P < 0.05); its average annual growth rate of TP was significantly higher than those without MS (1.0 vs 0.64 ml/yr, P < 0.05). TP average annual growth rate and IPSS score are found significantly correlated with blood glucose and triglyceride levels (P < 0.01). CONCLUSION: Metabolic syndrome affects the clinical progression in patients with BPH. Clinical attention should be paid.


Asunto(s)
Índice de Masa Corporal , Síndrome Metabólico/complicaciones , Hiperplasia Prostática/complicaciones , Anciano , Anciano de 80 o más Años , Glucemia , Presión Sanguínea , Humanos , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Hiperplasia Prostática/sangre , Hiperplasia Prostática/fisiopatología , Relación Cintura-Cadera
14.
Cancer Cell ; 35(3): 428-440.e5, 2019 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-30853353

RESUMEN

We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.


Asunto(s)
Fosfatidilinositol 3-Quinasa Clase I/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Perfilación de la Expresión Génica/métodos , Genómica/métodos , Receptor ErbB-2/genética , Neoplasias de la Mama Triple Negativas/clasificación , Pueblo Asiatico/genética , Biomarcadores de Tumor/genética , Cromosomas Humanos Par 22/genética , Variaciones en el Número de Copia de ADN , Femenino , Eliminación de Gen , Regulación Neoplásica de la Expresión Génica , Humanos , Mutación , Metástasis de la Neoplasia , Pronóstico , Neoplasias de la Mama Triple Negativas/genética
15.
Nat Commun ; 9(1): 1357, 2018 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-29636477

RESUMEN

Deregulation of the phosphoinositide 3-kinase (PI3K) pathway contributes to the development and progression of tumors. Here, we determine that somatic mutations in PIK3CA (44%), PIK3R1 (17%), AKT3 (15%), and PTEN (12%) are prevalent and diverse in Chinese breast cancer patients, with 60 novel mutations identified. A high proportion of tumors harbors multiple mutations, especially PIK3CA plus PIK3R1 mutations (9.0%). Next, we develop a recombination-based mutation barcoding (ReMB) library for impactful mutations conferring clonal advantage in proliferation and drug responses. The highest-ranking PIK3CA and PIK3R1 mutations include previously reported deleterious mutations, as well as mutations with unknown significance. These PIK3CA and PIK3R1 impactful mutations exhibit a mutually exclusive pattern, leading to oncogenesis and hyperactivity of PI3K pathway. The PIK3CA impactful mutations are tightly associated with hormone receptor positivity. Collectively, these findings advance our understanding of PI3K impactful mutations in breast cancer and have important implications for PI3K-targeted therapy in precision oncology.


Asunto(s)
Neoplasias de la Mama/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Regulación Neoplásica de la Expresión Génica , Mutación , Fosfatidilinositol 3-Quinasas/genética , Antineoplásicos/farmacología , Sitios de Unión , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase I/química , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Fosfatidilinositol 3-Quinasa Clase Ia , Doxorrubicina/farmacología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Modelos Moleculares , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/química , Fosfatidilinositol 3-Quinasas/metabolismo , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Estudios Retrospectivos , Transducción de Señal
16.
Asian Pac J Cancer Prev ; 18(7): 1769-1772, 2017 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-28749103

RESUMEN

Background: Cervical cancer is the most common gynecological malignant disorder worldwide. Activated platelets play a key role in cancer development and progression. Mean platelet volume (MPV) is an early indicator of platelet activation. The aim of the present study was to evaluate MPV levels in patients with cervical cancer. Materials and methods: A total of 181 patients with cervical cancer and 181 controls between January 2015 and June 2015 were included in the study. Patient characteristics and hematologic test data at initial diagnosis were collected and odds ratios (ORs) and 95% confidence intervals (CIs) for risk of cervical cancer were calculated using multivariate logistic regression analyses across MPV quartiles. Results: MPV levels were decreased in patients with cervical cancer compared with control subjects. A significant correlation between MPV and FIGO stage was found. Moreover, after adjusting for other risk factors, the ORs (95%CIs) for cervical cancer according to MPV quartiles were 4.450 (1.975-10.026), 2.505 (1.206-5.202), 0.573 (0.261-1.259), and 1.000, respectively. Conclusions: MPV was found to be independently associated with the presence of cervical cancer. Our results suggest that MPV could be potential diagnostic screening tool.

17.
J Thorac Dis ; 8(7): 1772-9, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27499968

RESUMEN

BACKGROUND: MicroRNA-361-5p (miR-361-5p) has been reported to be tumor suppressor in colorectal, gastric and prostate cancer, but as an oncogene in cervical cancer. No previous research has focused on the expression of miR-361-5p and its exact prognostic role in breast cancer (BC). METHODS: In this study, a tissue microarray (TMA)-based miRNA detection in situ hybridization (ISH) with LNA probe was used to detect miR-361-5p expression in 375 BC tissue. The expression level of miR-361-5p in BC and its potential prognostic value was investigated. RESULTS: Positive miR-361-5p staining was observed in 78.7% (N=295; 78.7% positive, 21.3% negative) in the 375 cases. The clinical outcome of patients with positive miR-361-5p expression [median disease-free survival (DFS) time 95.52 months] was significantly better than that of patients (median DFS time 82.33 months) with negative miR-361-5p expression (P=0.002). Moreover, the prognostic value of miR-361-5p was most significant among patients with triple-negative breast cancer (TNBC) for DFS (P=0.004). CONCLUSIONS: These results indicated that miR-361-5p expression is an independent predictive factor for better prognosis in BC.

18.
Oncotarget ; 7(40): 64900-64909, 2016 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-27588500

RESUMEN

MicroRNA-454 (miR-454) has been reported to play an oncogenic or tumor suppressor role in most cancers. However, the clinical relevance of miR-454 in breast cancer remains unclear. We examined the expression of miR-454 in a tissue microarray containing 534 breast cancer specimens from female patients at Fudan University Shanghai Cancer Center using in situ hybridization (ISH). Of these, 250 patients formed the training set and the other 284 were the validation set. The relationship between miR-454 and clinical outcome was analyzed by the Kaplan-Meier method. High expression of miR-454 indicated worse disease-free survival (DFS) in both cohorts (P = 0.006 for training set; P = 0.010 for validation set). Furthermore, in the triple-negative breast cancer (TNBC) subtype, miR-454 was positively correlated with worse clinical outcome (P = 0.013 for training set, P = 0.014 for validation set). In addition, patients in the low miR-454 expression cohort had better response to anthracycline compared to non-anthracycline chemotherapy (P = 0.056), but this difference was not observed in the high miR-454 expression cohort. Our findings indicated that miR-454 is a potential predictor of prognosis and chemotherapy response in TNBC.


Asunto(s)
Biomarcadores de Tumor/genética , MicroARNs/genética , Neoplasias de la Mama Triple Negativas/genética , Adulto , Antraciclinas/uso terapéutico , Antineoplásicos/uso terapéutico , Biomarcadores Farmacológicos , China , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Análisis de Matrices Tisulares , Resultado del Tratamiento , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/mortalidad
19.
Oncotarget ; 7(9): 9759-72, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26848770

RESUMEN

BACKGROUND: The tumor suppressor BRCA1 plays a pivotal role in maintaining genomic stability and tumor suppression. The BRCA1-A complex is required for recruitment of BRCA1 to DNA damage sites, DNA repair and cell cycle checkpoint control. Since germline mutations of BRCA1 often lead to breast tumors that are triple-negative breast cancer (TNBC) type, we aimed to investigate whether genetic deficiency in genes of the BRCA1-A complex is associated with risk to TNBC development. RESULTS: We found that rs7250266 in the promoter region of NBA1 confers a decreased risk to TNBC development, but not to non-TNBC susceptibility. In addition, the haplotypes containing two polymorphisms rs7250266 and rs2278256 are associated with a lower chance of TNBC development specifically. Our studies also showed that the protective alleles of rs7250266 (C > G) and rs2278256 (T > C) down-regulate promoter activity of NBA1 in mammary epithelial cells. METHODS: We investigated associations between the BRCA1-A complex genes and TNBC developing risk in first case-control study of Chinese Han Women population including 414 patients with TNBC and 354 cancer-free controls. We detected 37 common variants in ABRAXAS, RAP80, BRE, BRCC36 and NBA1/MERIT40 genes encoding the BRCA1-A complex and evaluated their genetic susceptibility to the risk of TNBC. An additional cohort with 652 other types of breast cancer (non-TNBC) cases and 890 controls was used to investigate the associations between TNBC-specific SNPs genotype and non-TNBCs susceptibility. CONCLUSIONS: Genetic variants in NBA1 may be an important genetic determinant of TNBC susceptibility. Further investigation and validation of these SNPs in larger cohorts may facilitate in predication and prevention of TNBC and in counseling individuals for risk of TNBC development.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Proteína BRCA1/genética , Predisposición Genética a la Enfermedad , Neoplasias de la Mama Triple Negativas/genética , Pueblo Asiatico/genética , Proteínas Portadoras/genética , Estudios de Casos y Controles , China , Daño del ADN/genética , Reparación del ADN/genética , Proteínas de Unión al ADN , Enzimas Desubicuitinizantes , Femenino , Chaperonas de Histonas , Humanos , Proteínas de la Membrana/genética , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple/genética , Riesgo , Neoplasias de la Mama Triple Negativas/epidemiología
20.
Clin Hemorheol Microcirc ; 59(4): 301-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-23988733

RESUMEN

BACKGROUND: The presence of silent cerebral infarction (SCI) increases the risk of transient ischemia attack, symptomatic stroke, cardiovascular disease and dementia. Increased viscosity is associated with aging, obesity, carotid intima-media thickness, metabolic syndrome, hypertension, diabetes, ischemic heart disease, and stroke. AIMS: The purpose of the study was to assess the hemorheological parameters levels in SCI patients. METHODS: A cross-sectional study was conducted to evaluate the association between hemorheological parameters and SCI in 1487 subjects (868 men and 619 women) undergoing medical check-up. RESULTS: The participants with SCI had higher whole blood viscosity (WBV) levels at low shear rate than those without SCI (10.34 ± 1.77 mPa.s vs. 8.98 ± 0.88 mPa.s; P <  0.001). Moreover, the subjects with a high WBV had a higher prevalence of SCI. Logistic regression analysis revealed that a significant association of WBV levels with the risk of SCI after adjustment for confounding factors (OR: 2.025; 95% CI: 1.750-2.343; P <  0.001). CONCLUSIONS: Whole blood viscosity at low shear rate is a novel indicator for SCI regardless of classical cardiovascular risk factors. Early measurement of whole blood viscosity may be helpful to assess the risk of stroke.


Asunto(s)
Viscosidad Sanguínea , Infarto Cerebral/sangre , Adulto , Infarto Cerebral/diagnóstico , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
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